16-Fluoro-11-deoxy-13-dihydro-prostaglandin

ABSTRACT

This disclosure describes novel 11-deoxy-13,14-dihydro-prostaglandin-9-ketals useful as bronchodilators and as gastric acid secretion inhibitors.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a division of application Ser. No. 475,479, filed June 3, 1974, now U.S. Pat. No. 3,932,463, which is a continuation-in-part of our copending application Ser. No. 263,036, filed June 15, 1972, which in turn is a continuation-in-part of our application Ser. No. 95,911, filed Dec. 7, 1970, both now abandoned.

BRIEF SUMMARY OF THE INVENTION

This invention relates to the novel 9-ketal derivatives of the prostanoic acids and esters. More specifically the compounds of this invention are all the optical antipodes, racemates, diastereoisomers, enantiomers, racemic mixtures and diastereomeric mixtures of the following general formulae: ##STR1## wherein X is an oxygen or sulfur atom; X' is an oxygen or sulfur atom; Y is a divalent moiety of the formulae ##STR2## wherein R₄ is hydrogen or alkanoyl and R₉ is hydrogen or lower alkyl with the proviso that when R₉ is lower alkyl then R₄ must be hydrogen; R is hydrogen, lower alkyl, or halo substituted lower alkyl; R₁ is hydrogen, fluorine, or lower alkyl; R₂ is alkyl having from two to seven carbon atoms; R₃ is hydrogen or alkyl having from one to 12 carbon atoms; R₅ is hydrogen, lower alkyl, or halo substituted lower alkyl; R₆ is hydrogen or lower alkyl; R₇ is hydrogen or lower alkyl; R₈ is hydrogen, fluorine, or lower alkyl; n is an integer from 4 to 8, inclusive; t is zero or 1 with the understanding that cyclic ketals are contemplated in all instances except that the moiety ##STR3## may also be a moiety of the formula: ##STR4## wherein R₁₀ is lower alkyl, aralkyl, or β, β, β-trihaloethyl.

Suitable lower alkyl and halo substituted lower alkyl groups contemplated by the present invention are those having up to four carbon atoms. Suitable alkanoyl groups are those having from two to 15 carbon atoms. Suitable aralkyl groups are benzyl, α-phenethyl, β-phenethyl, and the like, whereas halo is exemplified by fluoro, chloro and bromo.

A preferred embodiment of this invention are all the optical antipodes, racemates, diastereoisomers, enantiomers, racemic mixtures and diastereomeric mixtures of the following general formulae: ##STR5## wherein R, R₁,R₂,R₃,R₅,R₆,R₇,R₈,n,t, and Y are all as defined hereinabove.

DETAILED DESCRIPTION OF THE INVENTION

Also embraced within the scope of the present invention are the non-toxic, pharmaceutically acceptable salts of the novel compounds of the present invention when R₃ is hydrogen. The cations comprised in these salts include, for example, the non-toxic metal cations such as the sodium ion, potassium ion, calcium ion, and magnesium ion as well as the organic amine cations such as the tri(lower alkyl)amine cations (e.g., triethylamine, triethanolamine, procaine, and the like).

The prostaglandins are a family of closely related compounds which have been obtained from various animal tissues, and which stimulate smooth muscle, lower arterial blood pressure, antagonize epinephrine-induced mobilization of free fatty acids and have other pharmacological and autopharmacological effects in mammals. See Bergstrom et al., J. Biol. Chem., 238, 355 (1963); Horton, Experientia, 21, 113 (1965); and "The Prostaglandins" Vol. 1, ed. P. W. Ramwell, Plenum Press, New York, 1973, and references cited therein. All of the so called natural prostaglandins are derivatives of prostanoic acid: ##STR6## The hydrogen atoms attached to C-8 and C-12 are in trans-configuration. Substitution of C₁₅ with an oxy function creates a new assymetric center. In the natural mammalian prostaglandins this carbon atom is in the (S) configuration and is formulated as A, the (R) configuration being formulated as B. ##STR7## The natural prostaglandins represent only one of the possible optical isomers. The compounds of this invention include all possible optical isomers.

The novel compounds of this invention can be prepared from the corresponding 9-oxo-prostanoic acids or esters (I) by the usual techniques of ketalization involving treatment of the ketone with an excess of the requisite diol, dithiol, hydroxythiol (II) or alcohol in the presence of an acid catalyst. The preparation of the non-cyclic ketals can also be accomplished by treatment with the appropriate tri-alkyl or tri-aralkyl orthoformate in the presence of an acid catalyst. Introduction of a 15-alkyl group is accomplished by oxidation of the 15-hydroxy function in (in III, R₄ =hydrogen) and subsequent treatment with an alkyl Grignard or alkyl lithium reagent to give (V).

Saponification of esters represented by (III) or (V) by the usual technique provides the corresponding 15-hydroxy carboxylic acids. Conversely, it is possible to esterify the 15-hydroxy group in the usual manner, for example by treatment with an alkanoic acid anhydride in pyridine. The carboxylic acid function can be esterified by treatment with the appropriate diazoalkane, or by other methods well-known to the art.

In Flowsheet A which follows the formation of certain of the novel compounds of this invention is illustrated. In the Flowsheet R, R₁,R₂,R₃,R₄,R₅,R₆,R₇,R₈,R₉,X,X',n and t are as defined above. ##STR8##

The 16-fluoro and 16,16-difluoro 9-oxo-intermediates described herein above novel compounds and are useful as intermediates for the preparation of certain of the ketals of this invention. They as well as the corresponding 9-hydroxy derivatives have intrinsic utility as gastric acid secretion inhibitors, bronchodilators, and hypotensive agents and accordingly may be useful for the treatment of peptic ulcers, gastric hyperacidity, gastric erosion, bronchial asthma and hypertension. These novel optically active compounds have the following general formula and are to be considered as embraced within this invention. ##STR9## wherein R₃ is as defined hereinabove; Y' is a divalent moiety selected from the group consisting of ##STR10## wherein R₁₁ is hydrogen or a lower alkanoyl radical; R₁₀ is either hydrogen or fluorine; n' is an integer from 2 to 5, inclusive; and Z is a divalent moiety from the group consisting of ##STR11##

The novel compounds of the above general formula can be prepared by catalytic hydrogenation of the corresponding Δ¹⁰(11) -9-oxo derivatives, for example (V). ##STR12##

In the above synthetic sequence Y', R₃, n₁ and R₁₀ as hereinabove defined; R'₃ is an alkyl group of one to 12 carbon atoms. Hydrogenation of (V) is carried out in the usual fashion; rhodium-on-carbon is a useful catalyst. Saponification of the product (VI) to the prostenoic acid (VII) is usually effected where R'₃ is lower alkyl, preferably methyl. Sodium borohydride reduction of (VI) or (VII) provides a mixture of the 9α- and 9β-hydroxy derivatives, (VIII) and (IX), respectively. The diols are separable by the usual procedures of column chromatography. A more stereo-selective reduction of the 9α-ol (VIII) is possible with lithium perhydro-9b-boraphenalyl hydride (X) [H. C. Brown and W. C. Dickason, Journ. Amer. Chem. Soc., 92, 709 (1970)], or with lithium tri-sec-butylborahydride. The various esters and acids are obtainable by the usual methods of esterification, for example, with diazoalkanes, or saponification. The 15-O-alkanoyl derivatives are available by the usual techniques of hydroxy group acylation, e.g., treatment with acyl chloride in pyridine.

The novel compounds of the present invention are usually obtainable as oils having characteristic absorption spectra. They are relatively soluble in common organic solvents such as ethanol, ethyl acetate, dimethylformamide, and the like. The cationic salts of the compounds when R₃ is hydrogen are, in general, white to yellow crystalline solids having characteristic melting points and absorption spectra. They are relatively soluble in water, methanol, and ethanol but are relatively insoluble in benzene, diethyl ether, and petroleum ether.

The compounds of this invention can be isolated and purified by conventional methods. Isolation can be accomplished, for example, by dilution of the reaction mixture with water, extraction with a water-immiscible solvent such as methylene chloride, ethyl acetate, benzene, cyclohexane, ether, toluene and the like, chromatography, adsorption on ion-exchange resins, distillation, or a combination of these. Purification of the compounds of this invention can be accomplished by means known in the art for the purification of prostaglandins and lipids, fatty acids, and fatty esters. For example, reverse phase partition chromatography, countercurrent distribution, adsorption chromatography on acid washed Florisil (synthetic magnesium silicate), preparative paper chromatography, and combinations thereof can be used effectively to purify the compounds produced by the processes of this invention.

The racemic products and intermediates of this invention can be resolved into their optically active components by a number of methods of resolution well known in the art. For example, those compounds which are obtainable as free acids can be treated with an optically active base such as cinchonine, quinine, brucine, d- or l-α-phenylethylamine and the like to produce diastereoisomeric salts which can be separated by crystallization. Alternatively, the acid may be esterified with an optically active alcohol, e.g., d- or l-methanol, estradiol 3-acetate, etc., and the diastereoisomeric esters then resolved. Also, the 15-hydroxy function may be esterified with an optically active acid (e.g., d- or l-α-methoxy-α-trifluoromethylphenylacetic acid) and the resulting diastereoisomeric esters then separated by the usual techniques of fractional crystallization or chromatography. In more difficult instances it may be necessary to apply the technique of high speed liquid chromatography involving, if necessary, recycling techniques. [See G. Fallick, American Laboratory, 19-27 (August, 1973) as well as references cited therein. Additional information concerning high speed liquid chromatography and the instruments necessary for its application is available from Waters Associates, Inc., Maple Street, Milford, Mass.]. Another procedure would involve esterifying the 15-hydroxy function with a dibasic acid, such as phthalic acid, and treating the resulting phthalate acid-ester with an optically active base and separating the thus-formed diastereoisomeric salts by the usual procedures of fractional crystallization.

The resolution of the diastereoisomers or racemic mixtures of this invention can also be accomplished by reverse phase and absorption chromatography on an optically active support and adsorbent and by selective transformation of one isomer by microbiological or enzymatic means known to the art. Such transformations can be carried out by incubation or perfusion using methods well established in the art, followed by isolation and recovery of the isomer resistant to the metabolic transforamtion applied.

Individual diastereoisomers or racemates are also available by preparation from the corresponding resolved intermediates as illustrated in greater detail by the examples which follow. Also, compounds in which C₁₅ is substituted by hydroxy and hydrogen and is in either the S or R configuration can be converted to the opposite configuration by transforming the hydroxy function to a methanesulfonylate or p-toluenesulfonylate or the like, treating with a relatively non-basic oxy nucleophile, e.g., potassium acetate or sodium benzoate, and saponifying the thus-formed ester. Inversion of configuration takes plate on reaction with the oxy-nucleophile which procedes by an SN₂ displacement (Walden inversion). This transformation is illustrated in the following sequence. ##STR13##

Certain of the novel ketals of this invention are also useful for the preparation of other novel ketals of this invention as well as the novel 9-oxo-15 lower alkyl-15-hydroxy compounds that can be readily obtained from them by acid hydrolysis of the parent ketal. The ketal function then serves as a blocking group to allow the transformation of the secondary 15-hydroxy group to a tertiary hydroxy group via oxidation of the 15-ol followed by reaction with a lower alkyl magnesium halide.

The compounds of this invention are useful as bronchodilators for the treatment of asthma and chronic bronchitis. Bronchodilator activity is determined in guinea pigs against bronchospasms elicited by intravenous injections of 5-hydroxytryptamine, histamine or acetylcholine by the Konzett procedure. [See J. Lulling, P. Lievens, F. El Sayed and J. Prignot, Arzneimittel-Forschung, 18, 995 (1968).]

In Table A which follows bronchodilator activity for representative compounds of this invention against one or more of three spasmogenic agents is expressed as an ED₅₀ determined from the results obtained with three logarithmic cumulative intravenous doses.

                                      TABLE A                                      __________________________________________________________________________     Bronchodilator Activity (Konzett Assays) ED.sub.50, mg./kg.                    __________________________________________________________________________                  Spasmogenic Agent                                                 Compound     5-hydroxytryptamine                                                                        histamine                                                                              acetylcholine                                 __________________________________________________________________________     l-9,9-ethylenedioxy-                                                                        2.53 × 10.sup.-.sup.3                                                                376 × 10.sup.-.sup.6                                                             27.4 × 10.sup.-.sup.3                   15(S)-hydroxy-                                                                 prostanoic acid                                                                l-9,9-(1-methylethyl-                                                                        104 × 10.sup.-.sup.6                                                                 50 × 10.sup.-.sup.6                                                              644 × 10.sup.-.sup.6                   enedioxy)-15(S)-                                                               hydroxyprostanoic                                                              acid                                                                           __________________________________________________________________________

In Table A' which follows bronchodilator activity for representative compounds of this invention against one or more of three spasmogenic agents is reported. In this assay candidate compounds are suspended in 10% gum arabic solution and the suspension is administered by the intraduodenal route. The activity of the compound at any one dose is then investigated throughout the following hour (see above-cited reference, J. Lulling et al.). Potency is then reported as O, +, ++, +++, or ++++, wherein 0 represents no activity, + minimal activity and ++++ maximum activity.

                                      TABLE A'                                     __________________________________________________________________________                         Spasmogenic Agent                                                      Intraduodenal                                                                          5-Hydroxy    Acetyl-                                       Compound    Dose mg./kg.                                                                           tryptamine                                                                            Histamine                                                                            choline                                       __________________________________________________________________________     l 9,9-(2,2-di-                                                                 methyl-1,3-pro-                                                                pylenedioxy)-                                                                              10      +      +     +++                                           15(S)-hydroxy-                                                                 prostanoic acid                                                                l methyl 9,9-                                                                  ethylenedioxy-                                                                             10      ++     ++    ++                                            15(S)-hydroxy-                                                                 prostanoate                                                                    l 9,9-ethylene-                                                                oxythia-15(S)-                                                                             10      ++     +     ++                                            hydroxypro-                                                                    stanoic acid                                                                   l 9,9-(1,3-pro-                                                                pylenedioxy-                                                                               3.2     +      +++   +                                             15(S)-hydroxy-                                                                 prostanoic acid                                                                l methyl 9,9-(1,3-                                                             propylenedioxy)-                                                               15(S)-acetoxy-                                                                             10      ++     +     +++                                           prostanoate                                                                    l methyl 9,9-(1,2-                                                             dimethylethylene-                                                              dioxy)-15(S)-ace-                                                                          10      ++     ++    ++                                            toxyprostanoate                                                                l methyl-9,9-(1-                                                               chloromethyl-                                                                  ethylenedioxy)-                                                                            10      +++    +     ++                                            15(S)-acetoxy-                                                                 prostanoate                                                                    l 9,9-(1,2-di-                                                                 methylethylene-                                                                dioxy)-15(S)-                                                                  10          ++      +      +++                                                 hydroxyprostanoic                                                              acid                                                                           l 9,9-(1-chloro-                                                               methylethylene-                                                                            10      +++    +++   ++                                            dioxy)-15(S)-                                                                              3.2     ++++   ++    ++                                            hydroxyprostanoic                                                              acid                                                                           l methyl 9,9-(1-                                                               methylethylene-                                                                            10      +      ++    ++                                            dioxy)-15(S)-                                                                  acetoxyprostanoate                                                             __________________________________________________________________________

The novel ketals of this invention also show bronchodilator activity when administered by aerosol to dogs wherein bronchoconstriction was induced by administration of pilocarpine. In this assay, l 9,9-ethylenedioxy-15(S)-hydroxyprostanoic acid, a representative ketal of this invention, shows important advantages over the corresponding ketone, l 9-oxo-15(S)-hydroxyprostanoic acid. Thus at an aerosol concentration (0.032%) at which the activity of the ketone is very weak, the activity of the ketal is fully-present-indicating that the ketal is at least 10 times as potent as the ketone. In human ketal aerosol does not induce cough, although ketone aerosol does. This is very important since coughing is one of the damaging side effects reported in the literature when prostaglandin aerosols are administered to human subjects. [See Y. Kawakami et al., European Journal Clinical Pharmacology, 6, 127 (1973); M. F. Cuthbert, Brit. Med. Journ. 723 (Dec. 20, 1969); H. Herxheimer and I. Roetscher, European Journal Clinical Pharmacology, 3, 123 (1971).]

The compounds of this invention are also useful as inhibitors of gastric acid secretion and peptic ulcer formation and may be used for the treatment of gastric hyperacidity, gastric erosion, and peptic ulcer. Inhibition of basal gastric acid secretion can be determined by the following procedure.

Female Sprague-Dawley rats weighting 140-160 grams are fasted in individual cages for 18-24 hours. The rats are then lightly anesthetized with ether and their front teeth extracted to avoid destruction of the plastic cannula. A midline incision is then made and the stomach and duodenum exposed. A flanged polyvinyl tube is inserted into the fundic portion of the stomach and secured with a purse string suture line using 4-O Mersilene. The rat is then dosed by injection of the compound into the duodenum (1.0 ml. per 100 gram body weight). After dosing, the abdominal wall and skin are closed using metal wound clips. The rate is replaced in a cage containing a longitudinal slit to allow the polyvinyl tube to hang freely. An 8 ml. plastic collecting tube is attached to the flanged cannula and hangs freely below the cage. The first 30 minute sample is discarded designating this time as zero. The collecting tube is attached again and samples removed at the end of 60 and 120 minutes. These samples are referred to as "A" and "B" in the table. The hourly samples are then transferred to a 15 ml. centrifuge and centrifuged for 5-10 minutes. Total and sediment volume are then recorded with the supernatent volume being used as volume of secretion. A 1 ml. or less aliquot is then removed and placed in a 50 ml. beaker containing 10 ml. of distilled water. This sample is then titrated using 0.01N NaOH to pH 7.0 using a Beckman zeromatic pH meter. Volume, titratable acidity (meg.L) and total acid output (μeg/hour) are recorded. Percent inhibition is determined by comparison with the appropriate control. Groups of three rats were used for preliminary testing, and groups of six rats were used for dose-response evaluations. All compounds are administered in a vehicle consisting of 0.5% methocel, 0.4% tween 80, and saline at a constant volume of 1 ml./100 gram rat. Samples are dispersed by sonification. Percent inhibition is calculated on basis of concurrent vehicle control.

In Table B which follows is given the effect on total acid output after 120 minutes of a 10 mg./kg. dose of representative ketals of this invention. For comparison the result obtained with the corresponding 9-oxo derivative, l 9-oxo-15(S)-hydroxyprostanoic acid is included. It is to be noted that it is significantly less potent than the ketals.

                                      TABLE B                                      __________________________________________________________________________     Inhibition of Total Acid Output in the Acute Gastric Fistula                   __________________________________________________________________________     Rat                                                                              Compound                %-Inhibition of Total Acid                           (10 mg./kg., intraduodenal route)                                                                        Output After 120 Minutes                             __________________________________________________________________________     l 9-oxo-15(S)-hydroxyprostanoic acid                                                                     27                                                   (12.5 mg./kg. dose)                                                            l 9,9-ethylenedioxy-15(S)-hydroxyprostanoic                                                              63                                                   (acid                                                                          l 9,9-(1-methylethylenedioxy)-15(S)-hydroxy                                                              61                                                   prostanoic acid                                                                1 9,9-(1,2-dimethylethylenedioxy)-15(S)-                                                                 57                                                   hydroxy-prostanoic acid                                                        l methyl 9,9-(1,2-dimethylethylenedioxy)-15(S)-                                                          74                                                   acetoxyprostanoate                                                             l methyl 9,9-(1-chloromethylethylenedioxy)-                                                              26                                                   15(S)-acetoxyprostanoate                                                       l 9,9-(1-chloromethylethylenedioxy)-15(S)-                                                               99                                                   hydroxyprostanoic acid                                                         l methyl 9,9-propylenedioxy-15(S)-acetoxy                                                                60                                                   prostenoate                                                                    l 9,9-(2,2-dimethyl-1,3-propylenedioxy)-15(S)                                                            32                                                   hydroxyprostenoic acid                                                         l methyl 9,9-(2,2-dimethyl-1,3-propylenedioxy)-                                                          27                                                   15(S)-acetoxy-prostenoate                                                      l 9,9-ethyleneoxythia-15(S)-hydroxyprostanoic                                                            39                                                   acid                                                                           l methyl 9,9-ethylenedithia-15(S)-acetoxy-                                                               32                                                   prostanoate                                                                    l methyl 9,9-ethylenedioxy-15(S)-acetoxy-                                                                100                                                  prostanoate               (ED.sub.50 = 3.0 mg./kg.)                            __________________________________________________________________________

Dose response evaluation in the acute gastric fistual rat assay further illustrates the pronounced advantage of the novel ketals of this invention as gastric acid secretion inhibitors relative to the corresponding 9-oxo derivative. This is illustrated in Table C below wherein the ketals are as much as 17 times more potent then the ketone.

                                      TABLE C                                      __________________________________________________________________________     Inhibition of Total Acid Output in the Acute Gastric Fistula                   __________________________________________________________________________     Rat                                                                                                                         Ileal-Ligated Rat                                                              Assay                                                  ED.sub.50 (mg./kg., intraduodenal                                                                              Increase in                                    route of administration)                                                                               Intraduodenal                                                                          weight of                                      1 hr. collection (A)                                                                       2 hr. collection (B)                                                                       Dose mg./kg.                                                                           intestine.                __________________________________________________________________________     l 9-oxo-15(S)-hydroxyprostanoic                                                                     18          >25         10.0    1.02                      acid                                         5.0     0.1                       l 9,9-ethylenedioxy-15(S)-                                                                          1           2.3         10.0    0.46                      hydroxyprostanoic acid                       5.0     0.03                      l 9,9-(1,2-dimethylethylene-                                                                        <8          8           10.0    0.65                      dioxy-15(S)-hydroxy                          20.0    -0.4                      prostanoic acid                                                                l methyl 9,9-(1,2-dimethyl-                                                                         7           7           10.0    0.2                       ethylenedioxy)-15(S)-                        20.0    0.87                      acetoxy-prostanoate                                                            l 9,9-(1-chloromethylethylene-                                                                      6           6           10.0    0.33                      dioxy)-15(S)-hydroxy-                        20.0    -0.26                     prostanoic acid                                                                l methyl 9,9-(1,3-propylene-                                                                        6           6                                             dioxy)-15(S)-acetoxy-                                                          prostanoate                                                                    l methyl 9,9-ethylenedioxy-      3.0                                           l5(S)-acetoxy-prostanoate                                                      __________________________________________________________________________

An important consideration in the use of prostaglandin like substances for the inhibition of gastric acid secretion and the treatment of ulcers, etc. is that they do not at the same time induce diarrhea, a common phenomonen observed on administration of the prostaglandins. It is therefore unexpected and novel that in general, the compounds of this invention are not diarrheagenic at dose levels at which they are effective gastric acid secretion inhibitors. One measure of diarrheagenic potential is the ileal ligated rat assay, a description of which follows directly.

Female Sprague-Dawley rats (Charles River Laboratories) weighing less than 100 grams are fasted in individual cages for at least 18 hours. They are then anesthetized with ether and a midline incision made. The duodenum is exposed and the test drug or control injected intraduodenally. The ileocecal junction is then exposed and the terminal ileum is ligated using 3-0 silk thread just proximal to the junction. The incision is then closed using wound clips. Rats are placed back in individual cages without food or water for 4 hours. After this time the rats were sacrificed, the stomach and small intestine carefully removed, and cleaned of adherent mesentery. The removed portion of gut is then weighed to the nearest 0.1 gram. Compounds inducing diarrhea such as prostaglandins, cholera toxin, etc. produce an increase in weight of the ligated intestine. This increase from control is noted in Table C, as change in weight in grams after standardizing weights of gut to grams/100 gram rat.

When compound by this assay at effective gastric acid secretion inhibiting doses, as determined by the acute rat fistula assay, the novel ketals of Table C are non-diarrheagenic, whereas the corresponding ketone is diarrheagenic at 10 mg./kgg. dose, substantially lower than its ED₅₀ for inhibition of gastric acid secretion, see Table C.

Gastric acid secretion inhibition can also be observed in an assay wherein acid secretion is stimulated as in the well-known "Shay-rat" procedure, which is carried out in the following manner.

The rats (male, CFE strain) were starved for 48 hours (water was given ad libitum) to permit evacuation of stomach contents. On the morning of the experiment, under ether anesthesia, the abdominal region was shaved and a midline incision (1-11/2 inch) was made with a scapel. With the help of a closed curved hemostat the duodenum was picked up. Upon getting the duodenum into view, fingers were used to pull the stomach through the opening, the stomach was then gently manipulated with fingers to rid stomach of air and residual matter which were pushed through the pylorus. Two 5-inch sutures were drawn under the pyloric-duodenal puncture. A ligature, at the juncture, was formed with one of the threads. The second ligature was also formed but not tightened.

The test compound or the vehicle, usually 1 ml./100 g. body weight, were injected into the duodenum as close as possible to the first ligature. After injection the second ligature was tightened below the injection site to minimize leakage. The stomach was placed back through the opening into the abdominal cavity, the area of incision was washed with saline and the incision was closed with autoclips. (Occasionally, instead of an intraduodenal injection, animals were dosed by the oral or subcutaneous route. In the latter case, dosing was done 30 to 60 minutes before the operation.)

Three hours later, the rats were decapitated and exanguinated, taking care that blood did not drain into the esophagus. The abdominal cavity was exposed by cutting with scissors and the esophagus close to the stomach was clamped off with a hemostat, the stomach was removed by cutting above the hemostat (the esophagus was cut) and between the two sutures. Extraneous tissue was removed, the stomach washed with saline and blotted on gauze. A slit was carefully made in the stomach which was held over a funnel and the contents were collected in a centrifuge tube. The stomach was further cut along the outside edge and turned inside out. Two ml. distilled H₂ O were used to wash the stomach contents into the respective centrifuge tube. The combined stomach contents and wash were then centrifuged out for 10 minutes in the International Size 2 Centrifuge (setting at 30). The supernatant was collected, volume measured and recorded, 2 drops of a phenolphthalein indicator (1% in 95% ethanol) were added and the solution was tritrated with 0.02N NaOH (or with 0.04N NaOH when large volumes of stomach contents were encountered) to pH 8.4 (because of usual coloring of the stomach contents, phenolphthalein was only used to permit visual indication that the end point was near) and the amount of acid present was calculated.

Compouns inducing inhibition of gastric acid secretion of 20% or more were considered active. In a representative operation, and merely by way of illustration, the results obtained with this assay with a typical compound of the present invention are given in Table D below.

                  TABLE D                                                          ______________________________________                                                          Intraduodenal                                                                  Dose; mg./kg.                                                                               Percent                                          Compound         of body weight                                                                              Inhibition                                       ______________________________________                                         9,9-ethylenedioxy-                                                                              100          56                                               15-hydroxyprostanoic                                                           acid                                                                           ______________________________________                                    

This invention will be described in greater detail in conjunction with the following specific examples.

EXAMPLE 1 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(4-carbethoxybutyl)-cyclopentan-1-one

To a stirred solution of the sodium cyclopentanone carboxylate enolate in dimethoxyethane, prepared from 187 g. (1.248 moles) of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters), 52.4 g. (1.248 moles) sodium hydride (57.2% in mineral oil) and 1.6 1. of dimethoxyethane, is added dropwise 309 g. (1.212 moles) of ethyl 5-iodovalerate. The reaction mixture is stirred and heated at reflux for 18 hours. The mixture is cooled and filtered. The solvent is removed from the filtrate by evaportion and the residue is poured into dilute hydrochloric acid and extracted with ether. The combined extracts are washed with water and saline, dried over magnesium sulfate and evaporated to give an oil. The oil is distilled under reduced pressure to give 274 g. of a light yellow oil, b.p. 140°-143° C. (0.17 mm).

EXAMPLE 2 Preparation of 2-(4-carboxybutyl)cyclopentan-1-one

A stirred mixture of 274 g. of 2-carbalkoxy(mixed methyl and ethyl esters)-2-(4-carbethoxybutyl)cyclopentan-1-one (Example 1), 600 ml. of 20% hydrochloric acid and 325 ml. of acetic acid is heated at reflux for 20 hours. Solution occurs in approximately 1/2 hour. The solution is cooled and diluted with water and extracted with ether. The combined extracts are washed with saline and dried over magnesium sulfate and evaporated. The residue is evaporated twice with toluent to give 144 g. of an oil.

EXAMPLE 3 Preparation of 2-(4-carbethoxybutyl)cyclopentan-1-one

A stirred solution of 124 g. (0.673 mole) of 2-(4-carboxybutyl)cyclopentan-1-one (Example 2), 800 ml. of ethanol and 1 g. of p-toluenesulfonic acid monohydrate is heated at reflux for 18 hours. The solvent is evaporated and the residue is dissolved in ether. The ether solution is washed with saline, dilute sodium bicarbonate solution and again with saline, dried over magnesium sulfate and evaporated. The oil is distilled under reduced pressure to give 149 g. of a colorless oil, b.p. 106°-109° C. (0.23 mm).

EXAMPLE 4 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)-cyclopentan-1-one

In the manner described in Example 1, treatment of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters) with sodium hydride in dimethoxyethane followed by ethyl 4-iodobutyrate gives a yellow oil, b.p. 136°-137° C (0.16 mm).

EXAMPLE 5 Preparation of 2-(3-carboxypropyl)cyclopentan-1-one

In the manner described in Example 2, treatment of 2-carbalkoxy(mixed methyl and ethyl esters)-2-(3-carbethoxypropyl)cyclopentan-1-one (Example 4) with a 20% hydrochloric acid and acetic acid mixture gives a yellow oil.

EXAMPLE 6 Preparation of 2-(3-carbethoxypropylcyclopentan-1-one

In the manner described in Example 3, treatment of 2-(3-carboxypropyl)cyclopentan-1-one (Example 5) with p-toluene-sulfonic acid monohydrate in ethanol gives a colorless oil, b.p. 93° C (0.10 mm).

EXAMPLE 7 Preparation of ethyl and methyl 2-(6-carbethoxyhexyl)-1-cyclopentanon-2-carboxylate

In the manner described in Example 1, ethyl and methyl 2-cyclopentanone carboxylate is reacted with ethyl 7-bromoheptanoate to furnish the subject product, b.p. 147° C. (0.09 mm).

EXAMPLE 8 Preparation of 2-(6-carboxyhexyl)cyclopentan-1-one

In the manner described in Example 2, ethyl and methyl 2-(6-carbethoxyhexyl)-1-cyclopentanone-2-carboxylate (Example 7) is hydrolyzed to furnish the subject product, b.p. 143° C. (0.05 mm).

EXAMPLE 9 Preparation of 2-(6-carbethoxyhexyl)cyclopentan-1-one

In the manner described in Example 3, 2-(6-carboxyhexyl)cyclopentan-1-one (Example 8) is esterified to furnish the subject product, b.p. 110° C. (0.03 mm).

EXAMPLE 10 Preparation of 1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-one

A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)-cyclopentan-1-one (Example 9) in 250 ml. of acetic anhydride containing 0.940 g. of p-toluenesulfonic acid monohydrate is heated to boiling under partial reflux allowing distillate at 118° C. or less (i.e., acetic acid) to escape through a Vigreaux column equipped with a conductor to collect the distillate. After 16 hours, during which period acetic anhydride is added in portions in order to keep the solvent level at at least 100 ml., the solution is cooled and poured cautiously into a stirred cold mixture of saturated sodium bicarbonate solution (400 ml.) and hexane (250 ml.). The resulting mixture is stirred for an additional 30 minutes during which period solid sodium bicarbonate is added periodically to insure a basic solution. The hexane layer is separated and washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation of the residual oil gives 102 g. (87%) of pale yellow oil, b.p. 118° C. (0.07 mm).

EXAMPLE 11 Preparation of 1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-one

In the manner described in Example 10, treatment of 2-(3-carbethoxypropyl)cyclopentan-1-one (Example 6) with acetic anhydride and p-toluenesulfonic acid monohydrate gives a yellow oil, b.p. 98°-103° C. (0.35 mm).

EXAMPLE 12 Preparation of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-one

In the manner described in Example 10, treatment of 2-(4-carbethoxybutyl)cyclopentan-1-one (Example 3) with acetic anhydride and p-toluenesulfonic acid monohydrate gives a yellow oil, b.p. 109°-110° C. (0.37 mm).

EXAMPLE 13 Preparation of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 50 g. of 1-acetoxy-2-(6 -carboethoxyhexyl)cyclopent-1-one (Example 10) in 150 ml. of chloroform, 200 ml. of water and 18.8 g. of calcium carbonate, cooled in an ice bath, is added dropwise over a period of about 30 minutes, a solution of 30 g. of bromine in 50 ml. of carbon tetrachloride. After stirring for an additional 45 minutes the chloroform layer is separated and washed successively with dilute sodium thiosulfate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure.

The residual oil is dissolved in 50 ml. of N,N-dimethylformamide and added to a mixture of 33 g. of lithium bromide and 32 g. of lithium carbonate in 375 ml. of N,N-dimethylformamide, previously dried by refluxing with 375 ml. of benzene under a Dean-Stark apparatus followed by distillation of the benzene. The mixture is stirred at the reflux temperature for 30 minutes, then cooled and poured into 850 ml. of ice-cold water. The resulting mixture is acidified (cautiously) with 4N hydrochloric acid and extracted with ether three times. The combined ether extracts are washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure to afford 41.5 g. of an amber oil. In order to convert any isomeric material to the desired product, 41.5 g. of the above material is treated with 0.500 g. of p-toluenesulfonic acid monohydrate in 450 ml. of absolute alcohol at the reflux temperature for 18 hours. The solution is taken to dryness under reduced pressure. The resulting gum is dissolved in ether and washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure. The residual oil is distilled to give 30.2 g. of product; b.p. 118° C. (0.05 mm); λ_(max) ^(McOH) 229 mμ (ε9950); λ_(max) 5.75, 5.85, 6.15, 8.45 μ; vapor phase chromatography shows 99% product, containing 1% 2-(6-carbethoxyhexyl)cyclopentan-1-one.

This product can be purified by the following procedure. A mixture of 120 g. of 2-(6-carbethoxyhexyl)-2-cyclopentenone, containing approximately 5% of the saturated analogue, and 7.67 g. (10 mole percent) of p-carboxyphenylhydrazine in 400 ml. of absolute ethanol is stirred at ambient temperatures for 18 hours and is then refluxed for 1 hour. The mixture is cooled, the solvent is evaporated, and the residue is taken up into 150 ml. of chloroform and passed through a column of 450 g. of aluminum oxide (Merck). The filtrate is evaporated to yield a colorless oil containing <0.5% of the saturated impurity.

EXAMPLE 14 Preparation of 2-(3-carbethoxypropyl)cyclopent-2-en-1-one

In the manner described in Example 13, bromination of 1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-one (Example 11) followed by dehydrobromination with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 15 Preparation of 2-(4-carbethoxybutyl)cyclopent-2-en-1-one

In the manner described in Example 13, treatment of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-one (Example 12) with bromine and subsequent treatment of the brominated product with a mixture of lithium bromide and lithium carbonate in N,N-dimethylformamide is productive of the subject compound. Treatment of this product with p-carboxyphenylhydrazine by the procedure of Example 13 furnishes a product which contains less than 0.5% of the corresponding saturated ketone.

EXAMPLE 16 Preparation of 1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene

To a mixture of 35.97 g. (0.151 mole) of 2-(6-carbethoxyhexyl)-2-cyclopentenone (Example 13) and 15.0 g. (0.180 mole) of methoxyamine hydrochloride in 300 ml. of absolute ethanol is added 25 ml. of pyridine and the resulting solution is stirred for 20 hours at ambient temperatures. The solvent is evaporated and the residue is partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and the solvent is evaporated to yield an oil. Distillation yields 38.7 g. of a colorless oil, b.p. 115°-118° C. (0.075 mm). IR (film); 1740, 1627, 1053, 890 cm⁻ ¹. λ max (MeOH) 243 (13,000). NMRδ(CDCl₃): 3.89.

EXAMPLE 17 Preparation of 1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene

To an ice cooled solution of 34.10 g. (0.128 mole) of 1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene (Example 16) in 200 ml. of benzene under nitrogen is added dropwise 225 ml. of a 25% solution of diisobutyl aluminum hydride in hexane. The resulting solution is stirred for 2 hours at 0°-5° C., poured onto ice and dilute hydrochloric acid, and the aqueous phase is saturated with sodium chloride. The organic phase is separated, washed with saturated brine, dried (Na₂ SO₄), and evaporated to yield an oil. The latter is dissolved in 100 ml. of hot hexane and cooled to yield 24.3 g. of crystals, m.p. 62°-64° C. IR (KBr) 3260, 1630, 1059, 893 cm⁻ ¹. λ_(max) 243 (14,200). NMR (CDCl₃) δ: 2.37.

EXAMPLE 18 Preparation of 1-methoximino-2-(7-p-toluenesulfonyloxyheptyl)-2-cyclopentene

To a solution of 5.00 g. (0.0222 mole) of 1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene (Example 17) in 50 ml. of dry pyridine at 0° C. is added 8.45 g. (0.0444 mole) of p-toluene-sulfonyl chloride and the resulting solution is chilled at 5° C. overnight. The mixture is partitioned between 300 ml. of ice water and diethyl ether. The organic phase is washed with 1:1 ice cold hydrochloric acid, cold water, and cold saturated brine, dried (NaSO₄ /K₂ COhd 3), and evaporated under reduced pressure at room temperature to yield an oil. The latter is dissolved in 600 ml. of hexane, treated with 0.5 g. of Darco, filtered and evaporated to yield 7.7 g. of a colorless oil. IR (film) 1600, 1192, 1182, 1053, 890 cm⁻ ¹. λ_(max) (MeOH) 228 and 243.

EXAMPLE 19 Preparation of 1-methoximino-2-(8,8-dicarbethoxyoctyl)-2-cyclopentene

To an alcoholic solution of sodiodiethyl malonate, prepared from 0.847 g. (0.0368 g. atoms) of sodium, 100 ml. of absolute ethanol, and 7.05 g. (0.0440 mole) of diethyl malonate is added 7.7 g. of the tosylate of Example 18 and the mixture is refluxed for 2 hours under a nitrogen atmosphere. The mixture is partitioned between cold dilute hydrochloric acid and diethyl ether, and the organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to yield an oil. The excess diethyl malonate is distilled off under reduced pressure to yield 6.45 g. of a yellowish oil. IR (film) 1755, 1728, 1625, 1054, 890 cm⁻ ¹.

EXAMPLE 20 Preparation of 1-methoximine-2-(8,8-dicarboxyoctyl)-2-cyclopentene

A mixture of 6.45 g. of the diester of example 19 and 6.72 g. of potassium hydroxide in 150 ml. of 1:1 aqueous methanol is refluxed for 1 hour, cooled, and is partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with ether, and the organic phase is washed with water and saturated brine, dried (Na₂ SO₄) and evaporated to yield a solid. The solid is crystallized from benzene to yield 4.15 g. of tan crystals, m.p. 135°-137° C. (--CO₂).

EXAMPLE 21 Preparation of 1-methoximino-2-(8carboxyoctyl)-2-cyclopentene

A solution of 3.926 g.(0.0126 mole) of the diacid of Example 20 in 20 ml. of xylene is refluxed for 1.5 hours, cooled, and evaporated to yield a tan solid. IR (KBr) 1720, 1618, 1179, 1050, 986 cm⁻ ¹.

EXAMPLE 22 Preparation of 2-(8-carboxyoctyl)cycopent-2-en-1-one

The acid methoxime from Example 21 is refluxed for 5hours with 55 ml. of acetone and 20 ml. of 2N hydrochloric acid. The mixture is cooled, the solvent is evaporated, and the residue is partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to yield a tan solid. IR (KBr) 1745, 1665 cm⁻ ¹. λ_(max) (MeOH) 228 (12,600).

EXAMPLE 23 Preparation of 2-(8-carbethoxyoctyl)cyclopent-2-en-1-one

The acid ketone from Example 22 is Fisher esterified with 100 ml. of absolute ethanol, 100 ml. of benzene, and 20 mg. of p-toluenesulfonic acid for 6 hours, cooled, and the solvent is evaporated. The resulting oil is dissolved in 3:1 benzene-ether and the solution is passed through a column of 100 g. of Florisil. The filtrate is evaporated and the residue is distilled to yield 2.97 g. of a colorless oil, b.p. 137°-139° C. (0.05 Torr).

EXAMPLE 24 Preparation of 1-methoximine-2-(5-cyanopentyl)-2-cyclopentene

A mixture of 2.75 g. (0.01 mole of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 23) and 1.47 g. (0.03 mole) of sodium cyanide in 20 ml. of dry N,N-dimethylformamide is heated at 65°-70° C. for 3 hours. The cooled reaction mixture is poured into water and extracted with diethyl ether. The organic phase is washed with water and saturated saline solution, dried (MgSO₄), and evaporated to give 1.89 g. of a light yellow oil.

EXAMPLE 25 Preparation of 1-methoximine-2-(5-carboxypentyl)-2-cyclopentene

A mixture of 1.89 g. (0.0092 mole) of 1-methoximino

A mixture of 1.89 g. (0.0092 mole) of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene (Example 24) and 1 g. (0.025 mole) of sodium hydroxide in 50 ml. of 1:1 aqueous-ethanol is refluxed for 48 hours, cooled, and partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with diethyl ether, and the organic phase is washed with water and saturated saline solution, dried (MgSO₄), and evaporated to give 1.86 g. of a yellow oil.

EXAMPLE 26 Preparation of 2-(5-carboxypentyl)-2-cyclopentenone

A solution of 1.86 g. (0.00825 mole) 1-methoximino-2-(5-carboxypentyl)-2-cyclopentene (Example 25) in 44 ml. of acetone and 13.1 ml. of 2N hydrochloric acid is refluxed for 5 hours. The solvent is partially evaporated and a solid precipitates and is collected. The residue is extracted with diethyl ether and the organic phase is washed with saturated saline solution, dried (MgSO₄), and evaporated to yield additional solid. The combined solid material is crystallized from ether/pet ether (30°-60°C°) to yield crystalline material, m.p. 70°-72° C.

EXAMPLE 27 Preparation 2-(5-carbethoxypentyl)-2-cyclopentenone

A solution of 1.309 g. (0.00668 mole) of 2-(5-carboxypentyl)-2-cyclopentenone (Example 26) and 90 mg. of p-toluensulfonic acid in 150 ml. of ethanol is refluxed for 18 hours. The solvent is evaporated and the residue is dissolved in ether. The organic phase is washed with water, sodium bicarbonate solution, and saturated saline solution, dried (MgSO₄), and evaporated to give 1.371 g. of a light yellow oil.

EXAMPLE 28 Preparation of 2-(5-acetoxypentyl)-2-carbomethoxy/carbethoxy-cyclopentanone

A mixture of sodiocyclopentanone carboxylate, prepared from 1200 g. (8.0 mole) of cyclopentanone carboxylate (methyl and ethyl esters) and 200 g. (8.3 moles) of mineral oil free sodium hydride in 10 l. of 1,2-dimethoxyethane, 1320 g. (8.0 moles) of 5-chloro-1-amyl acetate [M.E. Synerholm, Journ. Amer. Chem. Soc., 69, 2681 (1947)], and 1200 g. (8.0 moles) of sodium iodide is refluxed under nitrogen for 18 hours. The mixture is cooled, concentrated to 4 1. and partitioned between dilute hydrochloric acid and diethyl ether. The organic phase is washed with water and saturated brine, dried (MgSO₄), and evaporated to yield 1920 g. of an oil.

EXAMPLE 29 Preparation of 2-(5-hydroxypentyl)cyclopentanone/2-(5-acetoxypentyl)-cyclopentanone

A mixture of 4,500 g. (16.2 moles) of 2-(5-acetoxypentyl)-2-carbomethoxy/carboethoxy-cyclopentanone (Example 28, 2.2 l. glacial acetic acid, 1 l. of concentrated hydrochloric acid, and 1 l. of water is refluxed for 18 hours, cooled, and partitioned between saturated brine and benzene. The organic phase is washed with saturated brine, dried (MgSO₄), and evaporated in vacuo to yield 3155 g. of an oil.

EXAMPLE 30 Preparation of 1-acetoxy-2-(5-acetoxypentyl)-1-cyclopentene

A solution of 400 g. (2.04 moles) of a mixture of 2-(5-hydroxypentyl)cyclopentanone and 2-(5-acetoxypentyl)cyclopentanone (Example 29) and 4.0 g. of p-toluenesulfonic acid monohydrate in 1 l. of acetic anhydride is refluxed at a rate to maintain a steady distillation of acetic acid from the reaction through a helix-packed fractionation column. The reaction is continued with the addition of acetic anhydride to maintain a constant volume until complete conversion of starting materials to product is evident. The mixture is cooled and partitioned between 2 l. of hexane and 3 l. of cold water containing solid sodium bicarbonate to maintain a neutral pH. The organic phase is washed with saturated brine, dried (MgSO₄), and evaporated to yield 452 g. of an oil.

EXAMPLE 31 Preparation of 2-(5-acetoxypentyl)-2-cyclopentenone

To a well stirred mixture of 405 g. (4.05 moles) of calcium carbonate, 3 l. of water, and 2.5 l. of chloroform cooled to 5° C. is added simultaneously 1016 g. (4.0 moles) of 1-acetoxy-2-(5-acetoxy-pentyl)-1-cyclopentene (Example 30) and a solution of 648 g. (4.05 moles) of bromine in 500 ml. of carbon tetrachloride at a rate to maintain a temperature below 10° C. The mixture is stirred for half an hour after addition of the reagents and the phases are then separated. The organic phase is washed with 2% sodium thiosulfate solution, water, and saturated brine, dried (MgSO₄), and evaporated in vacuo to an oil. The oil is immediately added to a refluxing slurry of 500 g. (5.0 moles) of calcium carbonate in 2.5 l of N,N-dimethylacetamide under nitrogen and the mixture is then refluxed for 30 minutes. The mixture is cooled, filtered, partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (MgSO₄), and evaporated to yield 757 g. of an oil, b.p. 116°-118° C. (0.25 mm.).

EXAMPLE 32 Preparation of 1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene

In the manner described for Example 16, 2-(5-acetoxypentyl)-2-cyclopentenone (Example 31) is treated with methoxyamine hydrochloride in pyridine and ethanol to yield the subject compound, b.p. 101°-103° C. (0.20 mm.).

EXAMPLE 33 Preparation of 1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene

A mixture of 74 g. (0.22 mole) of 1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene (Example 32) and 56 g. (1.0 mole) of potassium hydroxide in 300 ml. of 1:1 aqueous methanol is refluxed for 2 hours and then cooled. The solvent is partially removed in vacuo and the residue is partitioned between saturated brine and diethyl ether. The organic phase is washed with saturated brine, dried (MgSO₄), and evaporated to yield an oil which crystallized, m.p. 35°-36° C.

EXAMPLE 34 Preparation of 1-methoximine-2-(5-methanesulfonyloxypentyl)-2-cyclopentene

To a cold solution of 9.85 g. (0.05 mole) of 1-methoximino-2(5-hydroxypentyl)-2-cyclopentene Example 33) and 7.6 g. (0.075 mole) of triethylamine in 100 ml. of methylene chloride at -10° C. is added 6.3 g. (0.055 mole) of methanesulfonyl chloride at a rate to maintain a temperature of -10° to 0° C. The mixture is then stirred for 15 minutes and then poured into ice water. The organic phase is washed with cold 10% hydrochloric acid, cold saturated sodium bicarbonate solution, and cold saturated brine, dried (MgSO₄), and evaporated to yield a solid, m.p. 78°-80° C.

EXAMPLE 35 Preparation of 1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene

To a suspension of sodiodiethylmalonate in 1,2-dimethoxyethane, prepared from 248 g. (1.55 moles) of diethyl malonate and 17.2 g. (0.95 mole) of mineral oil free sodium hydride in 1 l. of 1,2-dimethoxyethane under nitrogen, is added 170 g. (0.62 mole) of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 34) in 1.5 l. of 1,2-dimethoxyethane and the mixture is refluxed for 5 hours. The mixture is cooled, filtered, and the solvent is evaporated. The residue is partitioned between cold dilute hydrochloric acid and water, and the organic phase is washed with saturated brine, dried (MgSO₄), and evaporated to remove solvent and excess diethyl malonate to yield 209 g. of an oil.

EXAMPLE 36 Preparation of 1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene

In the manner described in Example 20, 1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene is treated with potassium hydroxide in 1:1 aqueous methanol and then hydrochloric acid to yield the desired compound as crystals from diethyl ether, m.p. 110°-115° C.

EXAMPLE 37 Preparation of 1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene

A solution of 141 g. (0.50 mole) of 1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene in 500 ml. of bis-(2-methoxyethyl) ether is refluxed for 2 hours, cooled, and evaporated to yield an oil. The latter is crystallized from hexane to yield 92 g. of solid, m.p. 70°-72° C.

EXAMPLE 38 Preparation of 2-(6-carboxyhexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of 1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene (Example 37) with acetone and 2N hydrochloric acid at reflux provides the subject compound.

EXAMPLE 39 Preparation of 2-(6-carbethoxyhexyl)-2-cyclopentenone

Fischer estification of 2-(6-carboxyhexyl)-2-cyclopentenone (Example 38) in the manner of Example 23 provides the subject compound.

EXAMPLE 40 Preparation of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(7-p-toluenesulfonyloxy)-2-cyclopentene (Example 18) with sodium cyanide in the manner of Example 24 is productive of the subject compound.

EXAMPLE 41 Preparation of 2-(7-carboxyheptyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene (Example 40) by the procedure of Example 25 is productive of the subject compound.

EXAMPLE 42 Preparation of 2-(7-carboxyheptyl)-2-cyclopenten-1-one

Hydrolysis of the methoxime of Example 41 with acetone-hydrochloric acid by the procedure of Example 26 is productive of the subject compound.

EXAMPLE 43 Preparation of 2-(7-carbethoxyheptyl)-2-cyclopenten-1-one

Fisher estification of the carboxylic acid of Example 42 by the procedure of Example 27 is productive of the subject compound.

EXAMPLE 44 Preparation of 2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-one

A solution of 50 g. of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465 (1966)] in 1400 ml. of n-butanol containing 2.7 g. of p-toluenesulfonic acid monohydrate is allowed to stand at room temperature in a stoppered flask for about 24 hours. The solution is taken to dryness. The residue is taken up in ether and the ethereal solution is washed several times with saline solution, dried with anhydrous magnesium sulfate, and taken to dryness to afford the subject butyl ester.

EXAMPLES 45-47

Treatment of 2-(6-carboxyhexyl)cyclopent-2-en-1-one by the procedure of Example 44 with the appropriate alcohol affords the esters of the following table.

                                      TABLE I                                      __________________________________________________________________________     Example                                                                              Alcohol   Product Ester                                                  __________________________________________________________________________     45    isopropanol                                                                            2-(6-carboisopropoxyhexyl)cyclopent-2-                                         en-1-one                                                         46    methanol                                                                               2-(6-carbomethoxyhexyl)cyclopent-2-en-                                         1-one                                                            47    1-hydroxy-                                                                             2-(6-carbo-n-decyloxyhexyl)cyclopent-2-                                n-decane                                                                               en-1-one                                                         __________________________________________________________________________

EXAMPLE 48 Preparation of 3-(tert-butoxy)-1-iodooctane

Into a solution of 16.7 g. of 1-iodo-3-octanol [Shriner et al., J. Org. Chem. 4, 103 (1939)] in 250 ml. of methylene chloride is bubbled isobutylene at a fast rate until the solution is saturated. The solution is cooled and 2 ml. of concentrated sulfuric acid is added. The solution is stoppered and allowed to stand at room temperature for 3 days. After the solution is poured into 300 ml. of 5% sodium carbonate, the organic phase is separated, washed with brine, dried with anhydrous magnesium sulfate and evaporated to dryness. Distillation gave 13.9 g. (68%) of product, b.p. 59° C. (0.008 mm).

EXAMPLE 49 Preparation of 15-(tert-butoxy)-9-oxoprostanoic acid, ethyl ester

To a Grignard solution, prepared from 5.05 g. of magnesium and 65.8 g. of 3-(tert-butoxy)-1-iodooctane in 150 ml. of diethyl ether under nitrogen atmosphere, is added 4.0 g. of copper iodide-tri-n-butylphosphine complex followed by dropwise addition of 49 g. of 2-(6-cabethoxyhexyl)cyclopent-2-en-1-one [Hardegger et al., Helv. Chim. Acta 50, 2501 (1967)] and the resulting mixture is stirred for 18 hours. Saturated ammonium chloride (110 ml.) is added followed by 100 ml. of water and 100 ml. of diethyl ether. Unreacted magnesium is removed by filtration. The ethereal layer is washed successively with aqueous sodium thiosulfate solution, ammonium chloride solution, and water, dried over magnesium sulfate and taken to dryness to give an oil. Distillation at 0.05 mm. (bath 100°-185° C.) gives 45.4 g of material containing unreacted starting material and 30 g. (85% yield based on non-recovered starting material; see below) of residue which contains the desired product. This material is chromatographed on silica gel. The product is eluted with diethyl ether to give 25.2 g. (71% based on recovered starting material) of a syrup; this material has no significant ultraviolet absorption; λ_(max) ^(KBr) 5.74, 7.20, 7.35, 8.35 μ; nmr 2H quartet δ 4.09 (OCH₂ of ester), 1,H broad singlet 3.57 (carbinolic proton), 5H overlapping multiplets 2.0-2.4 (protons next to C=O). 3H triplet 1.22 (CH₃ of ethyl), 9H singlet 1.17 (CH₃ 's to t-butyl) and 3H triplet 0.9 (terminal methyl); mass spectrum: m/e 424

EXAMPLE 50 Preparation of 15-hydroxy-9-oxoprostanoic acid, ethyl ester

A solution of 25 g. of 15-(tert-butoxy)-9-oxoprostanoic acid, ethyl ester (Example 19) in 100 ml. of trifluoroacetic acid is stirred in an ice bath for 1 hour and is then poured into 500 ml. of ice water and extracted several times with chloroform. The combined chloroform extracts are washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and taken to dryness. The resulting oil is dissolved in 200 ml. of 1N ammonium hydroxide in ethanol, kept at ambient temperature for 15 minutes, then taken to dryness. The residual oil is dissolved in chloroform and washed with 1N hydrochloric acid, saturated sodium chloride solution, dried and taken to dryness to give 21.7 g. (100%) of product as a yellow syrup. There is essentially no uv absorption; λ_(max) ^(KBr) 2.90, 5.75, 8.45 μ; mnr 2H quartet δ 4.13 (OCH₂ of ester), 1H broad singlet 3.63 (carbinolic proton), 3H triplet (CH₃ of ester and 3H distorted triplet 0.92 (terminal methyl); mass spectrum: m/e 368.

EXAMPLE 51 Preparation of 15-hydroxy-9-oxoprostanoic acid

A suspension of 15 g. of 15-hydroxy-9-oxoprostanoic acid, ethyl ester (Example 50) in 230 ml. of aqueous methanol (1:1) containing 6.45 g. of potassium hydroxide is stirred at 50° C. for 1 hour and then at room temperature for 18 hours. The resulting solution is acidified with 1N hydrochloric acid, saturated with sodium chloride, and extracted several times wth diethyl ether. The combined ether extracts are washed twice with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and taken to dryness to give 13.1 g. (94%) of products as an oil. There is essentially no uv absorption; [α_(D) ²⁵ 0° (1.0% in CHCl₃); λ_(max) ^(KBr) 2.80-3.70 (broad), 5.75, 5.87 μ; nmr 2H singlet δ6.65 (hydroxyl and carboxyl protons), 1H broad singlet 3.63 (carbinolic proton), and 3H distorted triplet 0.93 (terminal methyl); mass spectrum: m/e 340.

EXAMPLE 52 Preparation of methyl 1-15 (S)-acetoxy-9-oxo-prostanoate

A solution of 2.5 g. of methyl 15(S)-acetoxy-9-oxo-5-cis, 10,13-trans-prostatrienoate [W.P. Schneider, R.D. Hamilton, L. E. Rhuland, Journ. Amer. Chem. Soc., 94, 2122 (1972)] in 150 ml. of ethyl acetate is hydrogenated using 5% rhodium-on-carbon catalyst. Removal of the catalyst by filtration followed by evaporation of the solvent gives 2.26 g. of subject compound as an oil; λ max 5.80 (carbonyl groups).

EXAMPLE 53 Preparation of methyl 1-15 (S)-hydroxy-9-oxo-prostanoate

A solution of 2.26 g. of methyl 15(S)-acetoxy-9-oxo-prostanoate (Example 52) in 300 ml. of absolute alcohol containing 790 mg. of potassium carbonate is stired at ambient temperature for 72 hours then concentrated to near dryness under reduced pressure. The resulting mixture is extracted with ether. The combined extracts are washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give 1.83 g. of an oil. Purfication by silica gel chromatography affords the suject compound as an oil; λ max. 2.92 (hydroxyl group), 5.74 μ (carbonyl groups); [α_(D) ²⁵ -23° C. (0.2% in CHCl₃).

EXAMPLE 54 Preparation of 1-15(S)-hydroxy-9-oxo-prostanoic acid

A solution of 930 mg. of methyl 15(S)-hydroxy-9-oxo-prostanoate (Example 53) in 16 ml. of methanol-water (1:1) containing 410 mg. of potassium hydroxide is stirred at ambient temperature for 18 hours. The solution is acidified with 1N hydrochloric acid and extracted with ether. The ether extract is washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and evaporated to dryness in vacuo to give 797 mg. of viscous oil; λ max 2.94-4.00 (broad) (hydroxyl and carboxyl groups), 5.80 (ketone carbonyl group), and 5.87 μ (acid carbonyl group); [α]_(D) ²⁵ - 23° C. (0.6% in CHCL₃).

EXAMPLE 55 Preparation of ethyl 9-ethylenedioxy-15-hydroxy-prostanoate

A solution of 3.4 g. of ethyl 15-hydroxy-9-oxo-prostanoate (Example 50) in 85 ml. of benzene containing 30 mg. of p-toluensulfonic acid monohydrate and 2 ml. of ethylene glycol is stirred at the reflux temperature for 18 hours. The water formed is removed by means of a Dean-Stark distilling receiver. The cooled solution is washed with 5% aqueous sodium carbonate solution, saturated sodium chloride solution, dried with anhydrous sodium sulfate and evaporated to dryness under reduced pressure to give 3.78 g. (99%) of oil; λ max. 2.93 (hydroxy group) and 5.77 β (ester carbonyl group).

EXAMPLE 56 Preparation of ethyl 9-ethylenedioxy-15-oxo-prostanoate

A solution of 8.7 g. of dry pyridine in 140 ml. of dry methylene chloride, stirred in a tap water bath is treated with 5.5 g. of dry chromium trioxide. The resulting deep red suspension is stirred at ambient temperature for 15 minutes. A solution of 3.78 g. of ethyl-9-ethylenedioxy-15-hydroxy-prostanoate (Example 55) in 15 ml. of methylene chloride is added, all at once, to the suspension. A black, tarry deposit is formed immediately. After stirring for 15 minutes at ambient temperature, the methylene chloride solution is decanted from the tarry deposit which is triturated with several portions of ether. The combined organic phases are washed with 5% aqueous sodium hydroxide, water, ice-cold 5% aqueous hydrochloric acid, saturated sodium bicarbonate solution, and saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give 3.29 g. (88%) of a viscous oil; λ max 5.78 and 5.86 μ (carbonyl groups).

EXAMPLE 57 Preparation of ethyl 9-ethylenedioxy- 15-hydroxy-15-methyl-prostanoate

To a Grignard solution prepared from 207 mg. of magnesium and 1.3 g. of methyl iodide in 10 ml. of ether under nitrogen atmosphere is added a solution of 1.77 g. of ethyl 9-ethylenedioxy-15-oxo-prostanoate (Example 56) in 10 ml. of ether and the resulting mixture is stirred at room temperature for 18 hours. Saturated ammonium chloride (20 ml.) is added followed by 10 ml. of water and 50 ml. of ether. The ethereal solution is washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give 1.77 g. (94%) of viscous oil; λ max. 2.94 (hydroxyl group) and 5.77 μ (carbonyl group).

EXAMPLE 58 Preparation of 9-ethylenedioxy-15-hydroxy-15-methyl-prostanoic acid

A solution of 1.33 g. of ethyl 9-ethylenedioxy-15-hydroxy-15-methyl prostanoate (Example 57) in 20 ml. of methanol-water (1:1) containing 500 mg. of potassium hydroxide is stirred at room temperature for 18 hours. The solution is neutralized with 30% aqueous sodium phosphate monobasic and extracted with ether. The ether extract is washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give 1.23 g. (99%) of viscous oil; λ max. 2.94-4.00 (broad) (hydroxyl and carboxyl groups) and 5.85 μ (acid carbonyl group).

EXAMPLE 59 Preparation of 3-(tert-butoxy-1iodohexane

A mixture of 23.4 g. of 1-chloro-3-hexanol [Fourneau, et al., Bull. Soc. Chem. France, 25, 367 (1919)] in 300 ml. of 2-butanone containing 30 g. of sodium iodide is stirred at the reflux temperature for 18 hours. The cooled solution is filtered and the mother liquor is taken to dryness. Distillation of the residue affords 32.9 (84%) of 1-iodo-3-hexanol, b.p. 105° C. (10 mm). Treatment of this material in 500 ml. of methylene chloride, containing 4 ml. of concentrated sulfuric acid, with isobutylene according to the procedure described in Example 48 gives 27 g. of crude material. Chromatography on florisil affords 16 g. of product; λ max. 7.22 and 7.37 μ (tert-butyl group).

EXAMPLE 60-78

Treatment of the various cyclopentenone esters listed in Table II below with the 3-t-butoxyalkyl magnesium iodide, also listed in the table, in the presence of tributylphosphine cuprous iodide complex all in the manner described in Example 49 above is productive of the 15-(tert-butoxy)-9-oxo-prostanoates of the table.

                                      TABLE 2                                      __________________________________________________________________________          Starting cyclo-                                                                pentenone of          Product                                             Example                                                                             Example   Grignard Reagent                                                                         15-(tert-butoxy)-9-oxo-prostanoates                   __________________________________________________________________________     60             3-t-butoxyhexyl                                                                          Ethyl 9-oxo-15-t-butoxy-19,20-dinor-                                 magnesium iodide                                                                         prostanoate                                           61   14        "         Ethyl 9-oxo-15-t-butoxy-5,6,7,19,20-                                           pentanor-prostanoate                                  62   15        "         Ethyl 9-oxo-15-t-butoxy-6,7,19,20-                                             tetranor-prostanoate                                  63   23        "         Ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-                                         19,20-dinor-prostanoate                               64   27        "         Ethyl 9-oxo-15-t-butoxy-7,19,20-trinor-                                        prostanoate                                           65   43        "         Ethyl 9-oxo-15-t-butoxy-7a-homo-19,20-                                         dinor-prostanoate                                     66   44        "         Butyl 9-oxo-15-t-butoxy-19,20-dinor-                                           prostanoate                                           67   45        "         Isopropyl 9-oxo-15-t-butoxy-19,20-dinor-                                       prostanoate                                           68   46        3-t-butoxyhexyl                                                                          Methyl 9-oxo-15-t-butoxy-19,20-dinor-                                magnesium iodide                                                                         prostanoate                                           69   47        "         Decyl 9-oxo-15-t-butoxy-19,20-dinor-                                           prostanoate                                           70   14        3-t-butoxyoctyl                                                                          Ethyl 9-oxo-15-t-butoxy-5,6,7-trinor-                                magnesium iodide                                                                         prostanoate                                           71   15        "         Ethyl 9-oxo-15-t-butoxy-6,7-dinor-                                             prostanoate                                           72   23        "         Ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-                                         prostanoate                                           73   27        "         Ethyl 9-oxo-15-t-butoxy-7-nor-prostanoate             74   43        "         Ethyl 9-oxo-15-t-butoxy-7a-homo-prostanoate           75   44        "         Butyl 9-oxo-15-t-butoxy-prostanoate                   76   45        "         Isopropyl 9-oxo-15-t-butoxy-prostanoate               77   46        "         methyl 9-oxo-15-t-butoxy-prostanoate                  78   47        "         decyl 9-oxo-15-t-butoxy-prostanoate                   __________________________________________________________________________

EXAMPLES 79-97

Treatment of the various 15-tert-butoxyprostanoates of Table 3 below with trifluoroacetic acid in the manner of Example 50 above is productive of the corresponding 15-hydroxyprostanoates of the table.

                                      TABLE 3                                      __________________________________________________________________________           Starting 15-tert-                                                              butoxyprostanoates                                                                           Product                                                    Example                                                                              of example  15-hydroxy-9-oxo-prostanoates                                __________________________________________________________________________     79    52          Ethyl 9-oxo-15-hydroxy-19,20-                                                  dinor-prostanoate                                            80    53          Ethyl 9-oxo-5-hydroxy-5,6,7,                                                   19,20-pentanor-prostanoate                                   81    54          Ethyl 9-oxo-15-hydroxy-6,7,19,                                                 20-tetranor-prostanoate                                      82    55          Ethyl 9-oxo-15-hydroxy-7a,7b-                                                  bishomo-19,20-dinor-                                                           prostanoate                                                  83    56          Ethyl 9-oxo-15-hydroxy-7,19,                                                   20-trinor-prostanoate                                        84    57          Ethyl 9-oxo-15-hydroxy-7a-                                                     homo-19,20-dinor-prostanoate                                 85    58          Butyl 9-oxo-15-hydroxy-19,20-                                                  dinor-prostanoate                                            86    59          Isopropyl 9-oxo-15-hydroxy-                                                    19,20-dinor-prostanoate                                      87    60          Methyl 9-oxo-15-hydroxy-                                                       19,20-dinor-prostanoate                                      88    61          Decyl 9-oxo-15-hydroxy-19,20-                                                  dinor-prostanoate                                            89    62          Ethyl 9-oxo-15-hydroxy-5,6,7-                                                  trinor-prostanoate                                           90    63          Ethyl 9-oxo-15-hydroxy-6,7-                                                    dinor-prostanoate                                            91    64          Ethyl 9-oxo-15-hydroxy-7a,7b-                                                  bishomo-prostanoate                                          92    65          Ethyl 9-oxo-15-hydroxy-7-nor-                                                  prostanoate                                                  93    66          Ethyl 9-oxo-15-hydroxy-7a-                                                     homo-prostanoate                                             94    67          Butyl 9-oxo-15-hydroxy-                                                        prostanoate                                                  95    68          Isopropyl 9-oxo-15-hydroxy-                                                    prostanoate                                                  96    69          Methyl 9-oxo-15-hydroxy-                                                       prostanoate                                                  97    70          Decyl 9-oxo-15-hydroxy-                                                        prostanoate                                                  __________________________________________________________________________

EXAMPLE 98 Preparation of l 20-ethyl-(15(S)-hydroxy-9-oxo-5-cis,10,13-trans-prostatrienoic acid

A solution of l 20-ethyl-9-oxo-11α,15(S)-bis-(tetrahydropyran-2-yloxy)-5-cis-13-trans-prostadienoic acid [Pat. No. 2,150,361 (West Germany, 1972)] in tetrahydrofuran containing 1.5 N hydrochloric acid is kept at ambient temperature for 70 hours. The solution is flooded with saturated sodium chloride and extracted several times with ether. The combined extracts are washed with water, dried with anhydrous magnesium sulfate and taken to dryness to afford the subject compound.

EXAMPLE 99 Preparation of l-methyl-15(S)-hydroxy-16(R)-methyl-9-oxo-5-cis,10,13-trans-prostatrienoat

An etheral solution containing a molar excess of diazomethane is added to a solution of l-15(S)-hydroxy-16(R)-methyl-9-oxo-5-cis,10,13-trans-prostatrienoic acid [M. Hayashi, et al., Jour. Org. Chem., 38, 1250 (1973)] in ether (or acetone). After 2 to 4 hours, the solution is carefully evaporated under reduced pressure and the material is purified in the usual way by chromatography on silica gel to afford the subject compound.

EXAMPLE 100 Preparation of ent-methyl-15-hydroxy-9-oxo-prostanoate

In the manner described in Example 99, treatment of ent-15-hydroxy-9-oxo-prostanoic acid [Bagli, J.F., et al., Tetrahedron Setters, No. 35, 3329 (1973)] with diazomethane provides the subject compound.

EXAMPLES 101-106

Treatment of an etheral solution of the various prostatrienoic acids listed in Table 5 below with etheral diazomethane in the usual manner is productive of the corresponding methyl prostatrienoates of the table.

                  TABLE 5                                                          ______________________________________                                         Ex-   Starting prosta-                                                                               Product Methyl prosta-                                   ample trienoic acids  trienoate                                                ______________________________________                                         101   15(S)-hydroxy-16-                                                                              Methyl l-15(S)-hydroxy-                                        (R)-methyl-9-oxo-                                                                              16(R)-methyl-9-oxo-5-                                          5-cis,10,13-    cis,10,13-trans-prosta-                                        trans-prostatri-                                                                               trienoate                                                      enoic acid.sup.1                                                         102   15(S)-hydroxy-16-                                                                              Methyl l-15(S)-hydroxy-                                        (S)-methyl-9-   16(S)-methyl-9-oxo-5-                                          oxo-5-cis,10,13-                                                                               cis,10,13-trans-prosta-                                        trans-prosta-   trienoate                                                      trienoic acid.sup.1                                                      103   15(R)-hydroxy-16-                                                                              Methyl l-15(R)-hydroxy-                                        (S)-methyl-9-oxo-                                                                              16(S)-methyl-9-oxo-5-                                          5-cis,10,13-    cis,10,13-trans-prosta-                                        trans-prosta-   trienoate                                                      trienoic acid.sup.1                                                      104   15(R)-hydroxy-16-                                                                              Methyl l-15(R)-hydroxy-                                        (R)-methyl-9-oxo-                                                                              16(R)-methyl-9-oxo-5-                                          5-cis,10,13-    cis,10,13-trans-prosta-                                        trans-prosta-   trienoate                                                      trienoic acid.sup.1                                                      105   15(S)-hydroxy-16,                                                                              Methyl l-15(S)-hydroxy-                                        16-dimethyl-9-  16,16-dimethyl-9-oxo-                                          oxo-5-cis,10,13-                                                                               5-cis,10,13-trans-                                             trans-prosta-   prostatrienoate                                                trienoic acid.sup.2                                                      106   l-20-Ethyl-15(S)-                                                                              Methyl l-20-ethyl-15(S)-                                       hydroxy-9-oxo-  hydroxy-9-oxo-5-cis,-                                          5-cis,10,13-    10,13-trans-prosta-                                            trans-prosta-   trienoate                                                      trienoic acid                                                                  (Example 98)                                                             ______________________________________                                          .sup.1 M. Hayashi, et al., Jour. Org. Chem., 38, 1250 (1973).                  .sup.2 Belgium Patent No. 782,822.                                       

EXAMPLES 107-112

Hydrogenation of the various prostenoic acid methyl esters listed in Table 6 below using 5% rhodium-on-carbon catalyst in ethyl acetate all in the manner described in Example 52 above is productive of the prostanoic acid methyl esters of the table.

                  TABLE 6                                                          ______________________________________                                               Starting prosteno-                                                             ic acid methyl  Product                                                  Ex-   esters of       Prostanoic acid methyl                                   ample Example         esters                                                   ______________________________________                                         107     101           Methyl l-15(S)-hydroxy-                                                        16(R)-methyl-9-oxo-                                                            prostanoate                                              108     102           Methyl l-15(S)-hydroxy-                                                        16(S)-methyl-9-oxo-                                                            prostenoate                                              109     103           Methyl l-15(R)-hydroxy-                                                        16(S)-methyl-9-oxo-                                                            prostanoate                                              110     104           Methyl l-15(R)-hydroxy-                                                        16(R)-methyl-9-oxo-                                                            prostanoate                                              111     105           Methyl l-15(S)-hydroxy-                                                        16,16-dimethyl-9-oxo-                                                          prostanoate                                              112     106           Methyl l-20-ethyl-15(S)-                                                       hydroxy-9-oxo-prostano-                                                        ate                                                      112A  dl-methyl 15-hy-                                                                               dl-methyl 15-hydroxy-9-                                        droxy-9-oxo-13- oxo-prostanoate                                                trans-prosteno-                                                                ate.sup.1                                                                112B  dl-methyl-15-   dl-methyl 15-epi-hydroxy-                                      epi-hydroxy-9-  9-oxoprostanoate                                               oxo-13-trans-                                                                  prostenoate.sup.1                                                        ______________________________________                                          .sup.1 K.F. Bernady and M.J. Weiss, Prostaglandins, 3, 505 (1973).       

EXAMPLES 113-272

Treatment of the various 9-oxo-prostanoates listed in Table 7 below with the indicated reagent, by the method described in Example 55 above, is productive of the ketals of the Table.

                                      TABLE 7                                      __________________________________________________________________________          Starting 9-oxo-                                                                             Ketalizing                                                                             Product                                              Example                                                                             prostanoates of Example                                                                     reagent Prostanoate Ketals                                   __________________________________________________________________________     113  79           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-19,20-dinor-prostanoate                      114  80           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-5,6,7-19,20-Pentanor-                                                  prostanoate                                          115  81           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-6,7,19,20-tetranor-                                                    prostanoate                                          116  82           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-7a,7b-bishomo-19,20-                                                   dinor-prostanoate                                    117  83           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-7,19,20-trinor-pros-                                                   tanoate                                              118  84           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-7a-homo-19,20-dinor-                                                   prostanoate                                          119  85           Ethylene                                                                               Butyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-19,20-dinor-prostanoate                      120  86           Ethylene                                                                               Isopropyl 9,9-(ethylenedioxy)-                                         glycol  15-hydroxy-19,20-dinor-pros-                                                   tenoate                                              121  87           Ethylene                                                                               Methyl 9,9-(ethylenedioxy)-15-                                         glycol  hydroxy-19,20-dinor-prostanoate                      122  88           Ethylene                                                                               Decyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-19,20-dinor-pros-                                                      tanoate                                              123  89           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-5,6,7-trinor-pros-                                                     tanoate                                              124  90           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-6,7,-dinor-pros-                                                       tonate                                               125  91           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-7a,7b-bishomo-                                                         prostanoate                                          126  92           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-7-nor-prostanoate                            127  93           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-7a-homo-prostanoate                          128  94           Ethylene                                                                               Butyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-prostanoate                                  129  95           Ethylene                                                                               Isopropyl 9,9-(ethylenedioxy)-                                         glycol  15-hydroxy-prostanoate                               130  96           Ethylene                                                                               Methyl 9,9-(ethylenedioxy)-                                            glycol  15-hydroxy-prostonate                                131  97           Ethylene                                                                               Decyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-prostanoate                                  132  50           Ethylene                                                                               Ethyl 9,9-(ethylenedioxy)-15-                                          glycol  hydroxy-prostanoate                                  133  Methyl l-15(R)-                                                                             Ethylene                                                                               Methyl l-9,9-(ethylenedioxy)-                             hydroxy-9-oxo-                                                                              glycol  15(R)-hydroxy-prostanoate                                 prostanoate [R.L.                                                              Spraggins, U. of                                                               Oklahoma, Disser-                                                              tation abs. 31,                                                                3934B (1971)]                                                             134  53           Ethylene                                                                               Methyl l-9,9-(ethylenedioxy)-                                          glycol  15(S)-hydroxy-prostanoate                            135  101          Ethylene                                                                               Methyl l-9,9-(ethylenedioxy)-                                          glycol  15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                          136  102          Ethylene                                                                               Methyl l-9,9-(ethylenedioxy)-                                          glycol  15(S)-hydroxy-16(S)-methyl-                                                    prostanoate                                          137  103          Ethylene                                                                               Methyl l-9,9-(ethylenedioxy)-                                          glycol  15(R)-hydroxy-16(S)-methyl-                                                    prostanoate                                          138  104          Ethylene                                                                               Methyl l-9,9-(ethylenedioxy)-                                          glycol  15(R)-hydroxy-16(R)-methyl-                                                    prostanoate                                          139  105          Ethylene                                                                               Methyl l-9,9(ethylenedioxy)-15(S)-                                     glycol  hydroxy-16,16-dimethylprostanoate                    140  106          Ethylene                                                                               Methyl l-20-ethyl-9,9-(ethylene-                                       glycol  dioxy)-15(S)-hydroxyprostanoate                      141  100          Ethylene                                                                               ent-Methyl 9,9-(ethylenedioxy)-                                        glycol  15-hydroxyprostanoate                                142  79           1,2-    Ethyl 15-hydroxy-9,9(1-methylethyl-                                    Propane-                                                                               enedioxy)-19,20-dinor-prostanoate                                      diol                                                         143  80           1,2-    Ethyl 15-hydroxy-9,9-(1-methyl-                                        Propane-                                                                               ethylenedioxy)-5,6,7-19,20-                                            diol    pentanor-prostanoate                                 144  81           1,2-    Ethyl 15-hydroxy-9,9-(1-methyl-                                        Propane-                                                                               ethylenedioxy)-6,7,19,20-                                              diol    tetranor-prostanoate                                 145  82           1,2-    Ethyl 15-hydroxy-9,9-(1-methyl-                                        Propane-                                                                               ethylenedioxy)-7a,7b-bishomo-                                          diol    19,20-dinor-prostanoate                              146  83           1,2-    Ethyl 15-hydroxy-9,9-(1-                                               Propane-                                                                               methylethylenedioxy)-7,19,                                             diol    20-trinor-prostanoate                                147  84           1,2-    Ethyl 15-hydroxy-9,9-(1-methyl-                                        Propane-                                                                               ethylenedioxy)-7a-homo-19,20-                                          diol    dinor-prostanoate                                    148  53           1,2-    Methyl l-15(S)-hydroxy-9,9-                                            Propane-                                                                               (1-methylethylendioxy)-                                                diol    prostanoate                                          149  101          1,2-    Methyl l-15(S)-hydroxy-16(R)-                                          Propane-                                                                               methyl-9,9-(1-methylethylene-                                          diol    dioxy)prostanoate.                                   150  102          1,2-    Methyl l-15(S)-hydroxy-16(S)-                                          Propane-                                                                               methyl-9,9-(1-methylethylene-                                          diol    dioxy)prostanoate                                    151  105          1,2-    Methyl l-15(S)-hydroxy-16,16-                                          diol    dioxy)prostanoate                                    152  85           2,3-    Butyl 9,9-(1,2-dimethylethyl-                                          Butane- enedioxy)-15-Hydroxy-19,20-                                            diol    dinor-prostanoate                                    153  86           2,3-    Isopropyl 9,9-(1,2-dimethyl-                                           Butane- ethylenedioxy)-15-hydroxy-                                             diol    19,20-dinor-prostanoate                              154  87           2,3-    Methyl 9,9-(1,2-dimethyl-                                              Butane- ethylenedioxy)-15-hydroxy-                                             diol    19,20-dinor-prostanoate                              155  88           2,3-    Decyl 9,9-(1,2-dimethylethyl-                                          Butane- enedioxy)-15-hydroxy-19,20-                                            diol    dinor-prostanoate                                    156  89           2,3-    Ethyl 9,9-(1,2-dimethylethyl-                                          Butane- enedioxy)-15-hydroxy-5,6,7-                                            diol    trinor-prostanoate                                   157  90           2,3-    Ethyl 9,9-(1,2-dimethylethyl-                                          Butane- enedioxy)-15-hydroxy-6,7-                                              diol    dinor-prostanoate                                    158  53           2,3-    Methyl l-9,9-(1,2-dimethyl-                                            Butane- ethylenedioxy)-15(S)-hydroxy-                                          diol    prostanoate                                          159  101          2,3-    Methyl l-9,9-(1,2-dimethyl-                                            Butane- ethylenedioxy)-15(S)-hydroxy-                                          diol    16(R)-methyl-prostanoate                             160  102          2,3-    Methyl l-9,9-(1,2-dimethyl-                                            Butane- ethylenedioxy)-15(S)-hydroxy-                                          diol    16(S)-methyl-prostanoate                             161  105          2,3-    Methyl l-9,9-(1,2-dimethyl-                                            Butane- ethylenedioxy)-15(S)-hydroxy-                                          diol    16,16-dimethyl-prostanoate                           162  91           1-chloro-                                                                              Ethyl-9,9-(1-chloromethylethyl-                                        2,3-    enedioxy)-15-hydroxy-7a,7b-                                            propane-                                                                               bishomo-prostanoate                                                    diol                                                         163  92           1-chloro-                                                                              Ethyl-9,9-(1-chloromethylethyl-                                        2,3-    enedioxy)-15-hydroxy-7-nor-                                            propane-                                                                               prostanoate                                                            diol                                                         164  93           1-chloro-                                                                              Ethyl 9,9-(1-chloromethylethyl-                                        2,3-    enedioxy)-15-hydroxy-7a-                                               propane-                                                                               homo-prostanoate                                                       diol                                                         165  94           1-chloro-                                                                              Butyl-9,9-(1-chloromethyl-                                             2,3-    ethylenedioxy)-15-hydroxy-                                             propane-                                                                               prostanoate                                                            diol                                                         166  95           1-chloro-                                                                              Isopropyl-9,9-(1-chloro-                                               2,3-    methylethylenedioxy)-                                                  propane-                                                                               15-hydroxy-prostanoate                                                 diol                                                         167  96           1-chloro-                                                                              Methyl-9,9-(1-chloromethyl-                                            2,3-    ethylenedioxy)-15-hydroxy-                                             propane-                                                                               prostanoate                                                            diol                                                         168  97           1-chloro-                                                                              Decyl 9,9-(1-chloromethylethyl-                                        2,3-    enedioxy)-15-hydroxy-prostanoate                                       propane-                                                                       diol                                                         169  53           1-chloro-                                                                              Methyl l-9,9-(1-chloromethyl-                                          2,3-    ethylenedioxy)-15(S)-hydroxy-                                          propane-                                                                               prostanoate                                                            diol                                                         170  101          1-chloro-                                                                              Methyl l-9,9-(1-chloro-                                                2,3-    methylethylenedioxy)-15(S)-                                            propane-                                                                               hydroxy-16(R)-methyl-                                                  diol    prostanoate                                          171  102          1-chloro-                                                                              Methyl l-9,9-(1-chloromethyl-                                          2,3-    ethylenedioxy)-15(S)-hydroxy-                                          propane-                                                                               16(S)-methyl-prostanoate                                               diol                                                         172  105          1-chloro-                                                                              Methyl l-9,9-(1-chloromethyl-                                          2,3-    ethylenedioxy)15(S)-hydroxy-                                           propane-                                                                               16,16-dimethyl-prostanoate                                             diol                                                         173  79           1,3-    Ethyl 15-hydroxy-9,9-(propyl-                                          propane-                                                                               enedioxy)-19,20-dionor-                                                diol    prostanoate                                          174  80           1,3-    Ethyl 15-hydroxy-9,9-(propyl-                                          propane-                                                                               enedioxy)-5,6,7,19,20-pentanor-                                        diol    prostanoate                                          175  81           1,3-    Ethyl 16-hydroxy-9,9-(propyl-                                          propane-                                                                               enedioxy)-6,7,19,20-tetranor-                                          diol    prostanoate                                          176  82           1,3-    Ethyl 15-hydroxy-9,9-(propyl-                                          propane-                                                                               enedioxy)-7a,7b-bishomo-19,20-                                         diol    dinor-prostanoate                                    177  83           1,3-    Ethyl 15-hydroxy-9,9-(propyl-                                          propane-                                                                               enedioxy)-7,19,20-trinor-                                              diol    prostanoate                                          178  84           1,3-    Ethyl 15-hydroxy-9,9-(propyl-                                          propane-                                                                               enedioxy)-7a-homo-19,20-dinor-                                         diol    prostanoate                                          179  85           1,3-    Butyl 15-hydroxy-9,9-(propyl-                                          propane-                                                                               enedioxy)-19,20-dinor-                                                 diol    prostanoate                                          180  86           1,3-    Isopropyl 15-hydroxy-9,9-                                              propane-                                                                               (propylenedioxy)-19,20-                                                diol    dinor-prostanoate                                    181  87           1,3-    Methyl 15-hydroxy-9,9-                                                 propane-                                                                               (propylenedioxy)-19,20-                                                diol    dinor-prostanoate                                    182  88           1,3-    Decyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-19,20-dinor-prostanoate                                         diol                                                         183  89           1,3-    Ethyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-5,6,7-trinor-prostanoate                                        diol                                                         184  90           1,3-    Ethyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-6,7-dinor-prostanoate                                           diol                                                         185  91           1,3-    Ethyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-7a,7b-bishomo-prostanoate                                       diol                                                         186  92           1,3-    Ethyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-7-nor-prostanoate                                               diol                                                         187  93           1,3-    Ethyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-7a-homo-prostanoate                                             diol                                                         188  94           1,3-    Butyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-prostanoate                                                     diol                                                         189  95           1,3-    Isopropyl 15-hydroxy-9,9-(propylene-                                   propane-                                                                               dioxy)-prostanoate                                   190  96           1,3-    Methyl 15-hydroxy-9,9-(propyl-                                         propane-                                                                               enedioxy)-prostanoate                                                  diol                                                         191  97           1,3-    Decyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-prostanoate                                                     diol                                                         192  50           1,3-    Ethyl 15-hydroxy-9,9-(propylene-                                       propane-                                                                               dioxy)-prostanoate                                                     diol                                                         193  Methyl l-15(R)-                                                                             1,3-    Methyl l-15(R)-hydroxy-9,9-                               hydroxy-9-oxo-                                                                              propane-                                                                               (propylenedioxy)-prostanoate                              prostanoate  diol                                                         194  53           1,3-    Methyl l-15(S)-hydroxy-9,9-                                            propane-                                                                               (propylenedioxy)-prostanoate                                           diol                                                         195  101          1,3-    Methyl l-15(S)-hydroxy-16(R)-                                          propane-                                                                               methyl-9,9-(propylenedioxy)-                                           diol    prostanoate                                          196  102          1,3-    Methyl l-15(S)-hydroxy-16(S)-                                          propane-                                                                               methyl-9,9-(propylenedioxy)-                                           diol    prostanoate                                          197  103          1,3-    Methyl l-15(R)-hydroxy-16(S)-                                          propane-                                                                               methyl-9,9-(propylenedioxy)-                                           diol    prostanoate                                          198  104          1,3-    Methyl l-15(R)-hydroxy-16(R)-                                          propane-                                                                               methyl-9,9-(propylenedioxy)-                                           diol    prostanoate                                          199  105          1,3-    Methyl l-15(S)-hydroxy-16,16-                                          propane-                                                                               dimethyl-9,9-(propylenedioxy)-                                         diol    prostanoate                                          200  106          1,3-    Methyl l-20-ethyl-15(S)-                                               propane-                                                                               hydroxy-9,9-(propylenedioxy)-                                          diol    prostanoate                                          201  100          1,3-    ent-Methyl 15-hydroxy-9,9-                                             propane-                                                                               (propylenedioxy)-prostanoate                                           diol                                                         202  79           2,2-    Ethyl 9,9-(2,2-dimethyl-                                               dimethyl-                                                                              propylenedioxy)-15-hydroxy-                                            1,3-pro-                                                                               19,20-dinor-prostanoate                                                panediol                                                     203  81           2,2-    Ethyl 9,9-(2,2-dimethyl-                                               dimethyl-                                                                              propylenedioxy)-15-hydroxy-                                            1,3-pro-                                                                               6,7,19,20-tetranor-                                                    panediol                                                                               prostanoate                                          204  88           2,2-    Decyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-19,20-                                            1,3-pro-                                                                               dinor-prostanoate                                                      panediol                                                     205  89           2,2-    Ethyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-5,6,7-                                            1,3-pro-                                                                               trinor-prostanoate                                                     panediol                                                     206  90           2,2-    Ethyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-6,7-                                              1,3-pro-                                                                               dinor-prostanoate                                                      panediol                                                     207  91           2,2-    Ethyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-7a,7b-                                            1,3-pro-                                                                               bishomo-prostanoate                                                    panediol                                                     208  92           2,2-    Ethyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-7-nor-                                            1,3-pro-                                                                               prostanoate                                                            panediol                                                     209  93           2,2-    Ethyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-7a-homo-                                          1,3-pro-                                                                               prostanoate                                                            panediol                                                     210  94           2,2-    Butyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-prostanoate                                       1,3-pro-                                                                       panediol                                                     211  97           2,2-    Decyl 9,9-(2,2-dimethylpropyl-                                         dimethyl-                                                                              enedioxy)-15-hydroxy-prostanoate                                       1,3-pro-                                                                       panediol                                                     212  53           2,2-    Methyl l-9,9-(2,2-dimethyl-                                            dimethyl-                                                                              propylenedioxy)-15(S)-hydroxy-                                         1,3-pro-                                                                               prostanoate                                                            panediol                                                     213  101          2,2-    Methyl l-9,9-(2,2-dimethyl-                                            dimethyl-                                                                              propylenedioxy)-15(S)-hydroxy-16-                                      1,3-pro-                                                                               (R)-methyl-prostanoate                                                 panediol                                                     214  105          2,2-    Methyl l-9,9-(2,2-dimethyl-                                            dimethyl-                                                                              propylenedioxy)-15(S)-hydroxy-                                         1,3-pro-                                                                               16,16-dimethyl-prostanoate                                             panediol                                                     215  79           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-15-                                         dithiol hydroxy-19,20-dinor-prostanoate                      216  80           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-15-                                         dithiol hydroxy-5,6,7,19,20-pentanor-                                                  prostanoate                                          217  81           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-15-                                         dithiol hydroxy-6,7,19,20-tetranor-                                                    prostanoate                                          218  82           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-15-                                         dithiol hydroxy-7a,7b-bishomo-19,20-                                                   dinor-prostanoate                                    219  83           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-7,19,20-trinor-                                                     prostanoate                                          220  84           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-7a-homo-19,20-                                                      dinor-prostanoate                                    221  85           1,2-Ethane-                                                                            Butyl 9,9-(ethylenedithia)-15-                                         dithiol hydroxy-19,20-dinor-prostanoate                      222  86           1,2-Ethane-                                                                            Isopropyl 9,9-(ethylenedithia)-                                        dithiol 15-hydroxy-19,20-dinor-                                                        prostanoate                                          223  87           1,2-Ethane-                                                                            Methyl 9,9-(ethylenedithia)-                                           dithiol 15-hydroxy-19,20-dinor-                                                        prostanoate                                          224  88           1,2-Ethane-                                                                            Decyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-19,20-dinor-                                                        prostanoate                                          225  89           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                          dithiol                                                                             15-hydroxy-5,6,7-trinor-                                                                            prostanoate                                          226  90           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-6,7-dinor-pros-                                                     tanoate                                              227  91           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-7a,7b-bishomo-                                                      prostanoate                                          228  92           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-7-nor-prostanoate                         229  93           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-7a-homo-prostanoate                       230  94           1,2-Ethane-                                                                            Butyl 9,9-(ethylenedithia)-15-                                         dithiol hydroxy-prostanoate                                  231  95           1,2-Ethane-                                                                            Isopropyl 9,9-(ethylenedithia)-                                        dithiol 15-hydroxy-prostanoate                               232  96           1,2-Ethane-                                                                            Methyl 9,9-(ethylenedithia)-                                           dithiol 15-hydroxy-prostanoate                               233  97           1,2-Ethane-                                                                            Decyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-prostanoate                               234  50           1,2-Ethane-                                                                            Ethyl 9,9-(ethylenedithia)-                                            dithiol 15-hydroxy-prostanoate                               235  Methyl l-15(R)-                                                                             1,2-Ethane-                                                                            Methyl l-9,9-(ethylenedithia)-                            hydroxy-9-oxo-                                                                              dithiol 15(R)-hydroxy-prostanoate                                 prostanoate                                                               236  53           1,2-Ethane-                                                                            Methyl l,9,9-(ethylenedithia)-                                         dithiol 15(S)-hydroxy-prostanoate                            237  101          1,2-Ethane-                                                                            Methyl l-9,9-(ethylenedithia)-                                         dithiol 15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                          238  102          1,2-Ethane-                                                                            Methyl l-9,9-(ethylenedithia)-                                         dithiol 15(S)-hydroxy-16(S)-methyl-                                                    prostanoate                                          239  103          1,2-Ethane-                                                                            Methyl l-9,9-(ethylenedithia)-                                         dithiol 15(R)-hydroxy-16(S)-methyl-                                                    prostanoate                                          240  104          1,2-Ethane-                                                                            Methyl l-9,9-(ethylenedithia)-                                         dithiol 15(R)-hydroxy-16(R)-methyl-                                                    prostanoate                                          241  105          1,2-Ethane-                                                                            Methyl l-9,9-(ethylenedithia)-                                         dithiol 15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                          242  106          1,2-Ethane-                                                                            Methyl l-20-ethyl-(9,9-ethyl-                                          dithiol enedithia)-15-hydroxyprostanoate                     243  100          1,2-Ethane-                                                                            ent-Methyl 9,9-(ethylenedithia)-                                       dithiol 15-hydroxy-prostanoate                               244  79           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-15-                                        ethanol hydroxy-19,20-dinor-prostanoate                      245  80           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-15-                                        ethanol 5,6,7,19,20-pentanor-prostanoate                     246  81           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-15-                                        ethanol hydroxy-6,7,19,20-tetranor-                                                    prostanoate                                          247  82           2-Mercapto-                                                                            Ethyl 9,9-(ethylenoxythia)-15-                                         ethanol hydroxy-7a,7b-bishomo-19,20-                                                   dinor-prostanoate                                    248  83           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-15-                                        ethanol hydroxy-7,19,20-trinor-prostano-                                               ate                                                  249  84           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-15-                                        ethanol hydroxy-7a-homo-19,20-dinor-                                                   prostanoate                                          250  85           2-Mercapto-                                                                            Butyl 9,9-(ethyleneoxythia)-15-                                        ethanol hydroxy-19,20-dinor-prostonate                       251  86           2-Mercapto-                                                                            Isopropyl 9,9-(ethyleneoxy-                                            ethanol thia)-15-hydroxy-19,20-dinor-                                                  prostanoate                                          252  87           2-Mercapto-                                                                            Methyl 9,9-(ethyleneoxythia)-                                          ethanol 15-hydroxy-19,20-dinor-                                                        prostanoate                                          253  88           2-Mercapto-                                                                            Decyl 9,9-(ethyleneoxythia)-                                           ethanol 15-hydroxy-19,20-dinor-                                                        prostanoate                                          254  89           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-                                           ethanol 15-hydroxy-5,6,7-trinor-                                                       prostanoate                                          255  90           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-                                           ethanol 15-hydroxy-6,7-dinor-                                                          prostanoate                                          256  91           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-                                           ethanol 15-hydroxy-7a,7b-bishomo-                                                      prostanoate                                          257  92           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-                                           ethanol 15-hydroxy-7-nor-prostanoate                         258  93           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-                                           ethanol 15-hydroxy-7a-homo-pros-                                                       tanoate                                              259  94           2-Mercapto-                                                                            Butyl 9,9-(ethyleneoxythia)-15-                                        ethanol hydroxy-prostanoate                                  260  95           2-Mercapto-                                                                            Isopropyl 9,9-(ethyleneoxythia)-                                       ethanol 15-hydroxy-prostanoate                               261  96           2-Mercapto-                                                                            Methyl 9,9-(ethyleneoxythia)-                                          ethanol 15-hydroxy-prostanoate                               262  97           2-Mercapto-                                                                            Decyl 9,9-(ethyleneoxythia)-                                           ethanol 15-hydroxy-prostanoate                               263  50           2-Mercapto-                                                                            Ethyl 9,9-(ethyleneoxythia)-15-                                        ethanol hydroxyprostanoate                                   264  Methyl l-15(R)-                                                                             2-Mercapto-                                                                            Methyl l-9,9-(ethyleneoxythia)-                           hydroxy-9-oxo-                                                                              ethanol 15(R)-hydroxy-prostanoate                                 prostanoate                                                               265  53           2-Mercapto-                                                                            Methyl l-9,9-(ethyleneoxythia)-                                        ethanol 15(S)-hydroxy-prostanoate                            266  101          2-Mercapto-                                                                            Methyl l-9,9-(ethyleneoxythia)-                                        ethanol 15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                          267  102          2-Mercapto-                                                                            Methyl l-9,9-ethyleneoxythia)-                                         ethanol 15(S)-hydroxy-16(S)-methyl-                                                    prostanoate                                          268  103          2-Mercapto-                                                                            Methyl l-9,9-(ethyleneoxythia)-15(R)-                                  ethanol hydroxy-16(S)-methyl-prostanoate                     269  104          2-Mercapto-                                                                            Methyl l-9,9-(ethyleneoxythia)-15-(R)-                                 ethanol hydroxy-16(R)-methyl-prostanoate                     270  105          2-Mercapto-                                                                            Methyl l-9,9-(ethyleneoxythia)-15(S)-                                  ethanol hydroxy-16,16-dimethyl-prostanoate                   271  106          2-Mercapto-                                                                            Methyl 20-ethyl-9,9-(ethyleneoxythia)-                                 ethanol 15(S)-hydroxy-prostanoate                            272  100          2-Mercapto-                                                                            ent-Methyl 9,9-(ethyleneoxythia)-15-                                   ethanol hydroxyprostanoate                                    272A                                                                               112A         Ethylene-                                                                              dl-methyl 9,9-(ethylenedioxy)-15-                                      glycol  hydroxyprostanoate                                    272B                                                                               112A         1,2-Pro-                                                                               dl-methyl 15-hydroxy-9,9-(1-methyl-                                    panediol                                                                               ethylenedioxy)prostanoate                             272C                                                                               112A         1-Chloro-                                                                              dl-methyl 9,9-(1-chloromethylethyl-                                    2,3-pro-                                                                               enedioxy)-15-hydroxyprostanoate                                        panediol                                                      272D                                                                               112A         2,3-Butane-                                                                            dl-methyl 9,9-(1,2-dimethylethylene-                                   diol    dioxyl)-15-hydroxyprostanoate                         272E                                                                               112A         1,3-Pro-                                                                               dl-methyl 15-hydroxy-9,9-(propylene-                                   panediol                                                                               dioxy)prostanoate                                     272F                                                                               112B         Ethylene-                                                                              dl-methyl 9,9-(ethylenedioxy)-15-epi-                                  glycol  hydroxyprostanoate                                    272G                                                                               112B         1,2-Pro-                                                                               dl-methyl 15-epi-hydroxy-9,9-(1-methyl-                                panediol                                                                               ethylenedioxy)prostanoate                             272H                                                                               112B         1-Chloro-                                                                              dl-methyl 9,9-(1-chloromethylethylene-                                 2,3-pro-                                                                               dioxy)-15-epi-hydroxyprostanoate                                       panediol                                                      272I                                                                               112B         2,3-Butane-                                                                            dl-methyl 9,9-(1,2-dimethylethylene-                                   diol    dioxy)-15-epi-hydroxyprostanoate                      272J                                                                               112B         1,3-Propane-                                                                           dl-methyl 15-epi-hydroxy-9,9-(propylene-                               diol    dioxy)prostanoate                                    __________________________________________________________________________

EXAMPLES 273-291

Treatment of the various 15-hydroxy-prostanate ketals of Table 8 below chromium trioxide in the manner of Example 56 above is productive of the corresponding 15-oxo-prostanoate ketals of the Table.

                  TABLE 8                                                          ______________________________________                                                 Starting 15-hy-                                                                               Product                                                         droxyprostanoate                                                                              15-oxo-prostanoate                                      Example ketals of example                                                                             ketals                                                  ______________________________________                                         273     113            Ethyl 9,9-(ethylene-                                                           dioxy)-15-oxo-19,20-                                                           dinor-prostanoate                                       274     114            Ethyl 9,9-(ethylene-                                                           dioxy)-15-oxo-5,6,7,                                                           19,20-pentanor-                                                                prostanoate                                             275     115            Ethyl 9,9-(ethylene-                                                           dioxy)-15-oxo-6,7,-                                                            19,20-tetranor-pros-                                                           tanoate                                                 276     145            Ethyl 9,9-(1-methyl                                                            ethylenedioxy)-15-                                                             oxo-7a,7b-bishomo-                                                             19,20-dinor-pros-                                                              tanoate                                                 277     146            Ethyl 9,9-(1-methyl-                                                           ethylenedioxy)-15-                                                             oxo-7,19,20-tri-                                                               nor-prostanoate                                         278     147            Ethyl 9,9-(1-methyl-                                                           ethylenedioxy)-15-                                                             oxo-7a-homo-19,20-                                                             dinor-prostanoate                                       279     152            Butyl 9,9-(1,2-di-                                                             methylethylenedi-                                                              oxy)-15-oxo-19,20-                                                             dinor-prostanoate                                       280     180            Isopropyl 15-oxo-                                                              9,9-(propylenedi-                                                              oxy)-19,20-dinor-                                                              prostanoate                                             281     181            Methyl 15-oxo-9,9-                                                             (propylenedioxy)-                                                              19,20-dinor-pros-                                                              tanoate                                                 282     182            Decyl 15-oxo-9,9-                                                              (propylenedioxy)-                                                              19,20-dinor-pros-                                                              tanoate                                                 283     205            Ethyl 9,9-(2,2-di-                                                             methylpropylenedi-                                                             oxy)-15-oxo-5,6,7-                                                             trinor-prostanoate                                      284     206            Ethyl 9,9-(2,2-di-                                                             methylpropylenedi-                                                             oxy)-15-oxo-6,7-di-                                                            nor-prostanoate                                         285     227            Ethyl 9,9-(ethyl-                                                              enedithia)-15-oxo-                                                             7a,7b-bishomo                                                                  prostanoate                                             286     228            Ethyl 9,9-(ethyl-                                                              enedithia)-15-oxo-                                                             7-nor-prostanoate                                       287     258            Ethyl 9,9-(ethyl-                                                              eneoxythia)-15-oxo-                                                            7a-homo-prostano-                                                              ate                                                     288     259            Butyl 9,9-(ethyl-                                                              eneoxythia)-15-oxo-                                                            prostanoate                                             289     260            Isopropyl 9,9-(eth-                                                            yleneoxythia)-15-                                                              oxo-prostanoate                                         290     261            Methyl 9,9-(ethyl-                                                             eneoxythia)-15-oxo-                                                            prostanoate                                             291     262            Decyl 9,9-(ethyl-                                                              eneoxythia)-15-oxo-                                                            prostanoate                                             ______________________________________                                    

EXAMPLES 292-310

Treatment of the various 15-oxo-prostanoate ketals of Table 9 below with methyl magnesium indole in the manner of Example 57 is productive of the corresponding 15-hydroxy-15-methyl-prostanoate ketals of the Table.

                  TABLE 9                                                          ______________________________________                                                 Starting 15-oxo-                                                                              Product                                                         prostanoate    15-hydroxy-15-                                                  ketals of      methyl-prostanoate                                      Example Example        ketals                                                  ______________________________________                                         292     273            Ethyl 9,9-(ethylene-                                                           dioxy)-15-hydroxy-                                                             15-methyl-19,20-                                                               dinor-prostanoate                                       293     274            Ethyl 9,9-(ethylene-                                                           dioxy)-15-hydroxy-                                                             15-methyl-5,6,7,19,                                                            20-pentanor-pros-                                                              tanoate                                                 294     275            Ethyl 9,9-(ethylene-                                                           dioxy)-15-hydroxy-                                                             15-methyl-6,7,19,-                                                             20-tetranor-pros-                                                              tanoate                                                 295     276            Ethyl 15-hydroxy-                                                              15-methyl-9,9-(1-                                                              methylethylene-                                                                dioxy)-7a,7b-bis-                                                              homo-19,20-dinor-                                                              prostanoate                                             296     277            Ethyl 15-hydroxy-                                                              15-methyl-9,9-(1-                                                              methylethylenedi-                                                              oxy)-7,19,20-tri-                                                              nor-prostanoate                                         297     278            Ethyl 15-hydroxy-                                                              15-methyl-9,9-(1-                                                              methylethylenedi-                                                              oxy)-7a-homo-19,20-                                                            dinor-prostanoate                                       298     279            Butyl 9,9-(1,2-di-                                                             methylethylenedi-                                                              oxy)-15-hydroxy-15-                                                            methyl-19,20-dinor-                                                            prostanoate                                             299     280            Isopropyl 15-hy-                                                               droxy-15-methyl-                                                               9,9-(propylenedi-                                                              oxy)-19,20-dinor-                                                              prostanoate                                             300     281            Methyl 15-hydroxy-                                                             15-methyl-9,9-                                                                 (propylenedioxy)-                                                              19,20-dinor-pros-                                                              tanoate                                                 301     282            Decyl 15-hydroxy-                                                              15-methyl-9,9-                                                                 (propylenedioxy)-                                                              19,20-dinor-pros-                                                              tanoate                                                 302     283            Ethyl 9,9-(2,2-di-                                                             methylpropylenedi-                                                             oxy)-15-hydroxy-15-                                                            methyl-5,6,7-tri-                                                              nor-prostanoate                                         303     284            Ethyl 9,9-(2,2-di-                                                             methylpropylenedi-                                                             oxy)-15-hydroxy-15-                                                            methyl-6,7-dinor-                                                              prostanoate                                             304     285            Ethyl 9,9-(ethyl-                                                              enedithia)-15-hy-                                                              droxy-15-methyl-                                                               7a,7b-bishomo-                                                                 prostanoate                                             305     286            Ethyl 9,9-(ethyl-                                                              enedithia)-15-hy-                                                              droxy-15-methyl-7-                                                             nor-prostanoate                                         306     287            Ethyl 9,9-(ethyl-                                                              eneoxythia)-15-hy-                                                             droxy-15-methyl-                                                               7a-homo-prostano-                                                              ate                                                     307     288            Butyl 9,9-(ethyl-                                                              eneoxythia)-15-hy-                                                             droxy-15-methyl-                                                               prostanoate                                             308     289            Isopropyl 9,9-                                                                 (ethyleneoxythia)-                                                             15-hydroxy-15-                                                                 methyl-prostanoate                                      309     290            Methyl 9,9-(ethyl-                                                             eneoxythia)-15-hy-                                                             droxy-15-methyl-                                                               prostanoate                                             310     291            Decyl 9,9-(ethyl-                                                              eneoxythia)-15-hy-                                                             droxy-15-methyl-                                                               prostanoate                                             ______________________________________                                    

EXAMPLES 311-430

Saponification of the various prostanoate ketals of Table 10 below in the manner of Example 58 above is productive of the prostanoic acid ketals of the Table.

                  TABLE 10                                                         ______________________________________                                               Starting prostan-                                                        Ex-   oate ketals of                                                                               Product                                                    ample example       Prostanoic acid ketals                                     ______________________________________                                         311   113           9,9-(ethylenedioxy)-                                                           15-hydroxy-19,20-                                                              dinor-prostanoic acid                                      312   114           9,9-(ethylenedioxy)-                                                           15-hydroxy-5,6,7,19,-                                                          20-pentanor-prostanoic                                                         acid                                                       313   115           9,9-(ethylenedioxy)-15-                                                        hydroxy-6,7,19,20-                                                             tetranor-prostanoic                                                            acid                                                       314   116           9,9-(ethylenedioxy)-15-                                                        hydroxy-7a,7b-bis-                                                             homo-19,20-dinor-                                                              prostanoic acid                                            315   117           9,9-(ethylenedioxy)-                                                           15-hydroxy-7,19,20-                                                            trinor-prostanoic                                                              acid                                                       316   118           9,9-(ethylenedioxy)-                                                           15-hydroxy-7a-homo-                                                            19,20-dinor-prostanoic                                                         acid                                                       317   123           9,9-(ethylenedioxy)-15-                                                        hydroxy-5,6,7-trinor-                                                          prostanoic acid                                            318   124           9,9-(ethylenedioxy)-15-                                                        hydroxy-6,7-dinor-                                                             prostanoic acid                                            319   125           9,9-(ethylenedioxy)-15-                                                        hydroxy-7a,7b-bis-                                                             homo-prostanoic acid                                       320   126           9,9-(ethylenedioxy)-15-                                                        hydroxy-7-nor-                                                                 prostanoic acid                                            321   127           9,9-(ethylenedioxy)-                                                           15-hydroxy-7a-homo-                                                            prostanoic acid                                            322   132           9,9-(ethylenedioxy)-15-                                                        hydroxy-prostanoic                                                             acid                                                       323   133           l-9,9-(ethylenedioxy)-                                                         15(R)-hydroxy-                                                                 prostanoic acid                                            324   134           l-9,9-(ethylenedioxy)-                                                         15(S)-hydroxy-                                                                 prostanoic acid                                            325   135           l-9,9-(ethylenedioxy)-                                                         15(S)-hydroxy-16(R)-                                                           methyl-prostanoic                                                              acid                                                       326   136           l-9,9-(ethylenedioxy)-                                                         15(S)-hydroxy-16(S)-                                                           methyl-prostanoic acid                                     327   137           l-9,9-(ethylenedioxy)-                                                         15(R)-hydroxy-16(S)-                                                           methyl-prostanoic acid                                     328   138           l-9,9-(ethylenedioxy)-                                                         15(R)-hydroxy-16(R)-                                                           methyl-prostanoic acid                                     329   139           l-9,9-(ethylenedioxy)-                                                         15(S)-hydroxy-16,16-                                                           dimethyl-prostanoic                                                            acid                                                       330   140           l-20-ethyl-9,9-(ethyl-                                                         enedioxy)-15(S)-hydroxy-                                                       prostanoic acid                                            331   141           ent-9,9-(ethylene-                                                             dioxy)-15-hydroxy-                                                             prostanoic acid                                            332   142           15-hydroxy-9,9-(1-meth-                                                        ylethylenedioxy)-19,20-                                                        dinor-prostanoic acid                                      333   143           15-hydroxy-9,9-(1-meth-                                                        ylethylenedioxy)-5,6,7,                                                        19,20-pentanor-                                                                prostanoic acid                                            334   144           15-hydroxy-9,9-(1-meth-                                                        ylethylenedioxy)-6,7-                                                          19,20-tetranor-pros-                                                           tanoic acid                                                335   145           15-hydroxy-9,9-(1-meth-                                                        ylethylenedioxy)-7a,7b-                                                        bishomo-19,20-dinor-                                                           prostanoic acid                                            336   146           15-hydroxy-9,9-(1-meth-                                                        ylethylenedioxy)-7,19,-                                                        20-trinor-prostanoic                                                           acid                                                       337   147           15-hydroxy-9,9-(1-meth-                                                        ylethylenedioxy)-7a-                                                           homo-19,20-dinor-                                                              prostanoic acid                                            338   148           l-15(S)-hydroxy-9,9-                                                           (1-methylethylenedioxy)-                                                       prostanoic acid                                            339   149           l-15(S)-hydroxy-16(R)-                                                         methyl-9,9-(1-methyl-                                                          ethylenedioxy)-pros-                                                           tanoic acid                                                340   150           l-15(S)-hydroxy-16(S)-                                                         methyl-9,9-(1-methyl-                                                          ethylenedioxy)-pros-                                                           tanoic acid                                                341   151           l-15(S)-hydroxy-16,16-                                                         dimethyl-9,9-(1-methyl-                                                        ethylenedioxy)-                                                                prostanoic acid                                            342   152           9,9-(1,2-dimethylethyl-                                                        enedioxy)-15-hydroxy-                                                          19,20-dinor-pros-                                                              tanoic acid                                                343   156           9,9-(1,2-dimethylethyl-                                                        enedioxy)-15-hydroxy-                                                          5,6,7-trinor-pros-                                                             tanoic acid                                                344   157           9,9-(1,2-dimethylethyl-                                                        enedioxy)-15-hydroxy-                                                          6,7-dinor-prostanoic                                                           acid                                                       345   158           l-9,9-(1,2-dimethyl-                                                           ethylenedioxy)-15(S)-                                                          hydroxy-prostanoic                                                             acid                                                       346   159           l-9,9-(1,2-dimethyl-                                                           ethylenedioxy)-15(S)-                                                          hydroxy-16(R)-methyl-                                                          prostanoic acid                                            347   160           l-9,9-(1,2-dimethyl-                                                           ethylenedioxy)-15(S)-                                                          hydroxy-16(S)-methyl-                                                          prostanoic acid                                            348   161           l-9,9-(1,2-dimethyl-                                                           ethylenedioxy)-15(S)-                                                          hydroxy-16,16-dimethyl-                                                        prostanoic acid                                            349   162           9,9-(1-chloromethyl-                                                           ethylenedioxy)-15-                                                             hydroxy-7a,7b-bis-                                                             homo-prostanoic acid                                       350   163           9,9-(1-chloromethyl-                                                           ethylenedioxy)-15-                                                             hydroxy-7-nor-pros-                                                            tanoic acid                                                351   164           9,9-(1-chloromethyl-                                                           ethylenedioxy)-15-                                                             hydroxy-7a-homo-                                                               prostanoic acid                                            352   165           9,9-(1-chloromethyl-                                                           ethylenedioxy)-15-                                                             hydroxy-prostanoic                                                             acid                                                       353   169           l-9,9-(1-chloromethyl-                                                         ethylenedioxy)-15(S)-                                                          hydroxy-prostanoic                                                             acid                                                       354   170           l-9,9-(1-chloromethyl-                                                         ethylenedioxy)-15(S)-                                                          hydroxy-16(R)-methyl-                                                          prostanoic acid                                            355   171           l-9,9-(1-chloromethyl-                                                         ethylenedioxy)-15(S)-                                                          hydroxy-16(S)-                                                                 methyl-prostanoic acid                                     356   172           l-9,9-(1-chloromethyl-                                                         ethylenedioxy)-15(S)-                                                          hydroxy-16,16-di-                                                              methyl-prostanoic acid                                     357   173           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-19,20-                                                            dinor-prostanoic acid                                      358   174           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-5,6,7,19,-                                                        20-pentanor-prostan-                                                           oic acid                                                   359   175           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-6,7,19,20-                                                        tetranor-prostanoate                                       360   176           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-7a,7b-                                                            bishomo-19,20-dinor-                                                           prostanoic acid                                            361   177           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-7,19,20-                                                          trinor-prostanoic acid                                     362   178           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-7a-homo-                                                          19,20-dinor-prostanoic                                                         acid                                                       363   183           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-5,6,7-                                                            trinor-prostanoic acid                                     364   184           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-6,7-dinor-                                                        prostanoic acid                                            365   185           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-7a,7b-bis-                                                        homo-prostanoic acid                                       366   186           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-7-nor-                                                            prostanoic acid                                            367   187           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-7a-homo-                                                          prostanoic acid                                            368   188           15-hydroxy-9,9-(pro-                                                           pylenedioxy)-prostanoic                                                        acid                                                       369   193           l-15(R)-hydroxy-9,9-                                                           (propylenedioxy)-                                                              prostanoic acid                                            370   194           l-15(S)-hydroxy-9,9-                                                           (propylenedioxy)-                                                              prostanoic acid                                            371   195           l-15(S)-hydroxy-16(R)-                                                         methyl-9,9-(propylene-                                                         dioxy)-prostanoic acid                                     372   196           l-15(S)-hydroxy-16(S)-                                                         methyl-9,9-(propylene-                                                         dioxy)-prostanoic acid                                     373   197           l-15(R)-hydroxy-16(S)-                                                         methyl-9,9-(propylene-                                                         dioxy)-prostanoic acid                                     374   198           l-15(R)-hydroxy-16(R)-                                                         methyl-9,9-(propyl-                                                            enedioxy)-prostanoic                                                           acid                                                       375   199           l-15(S)-hydroxy-16,16-                                                         dimethyl-9,9-(propyl-                                                          enedioxy)-prostanoic                                                           acid                                                       376   200           l-20-ethyl-15(S)-                                                              hydroxy-9,9-(propylene-                                                        dioxy)-prostanoic acid                                     377   201           ent-15-hydroxy-9,9-                                                            (propylenedioxy)-                                                              prostanoic acid                                            378   202           9,9-(2,2-dimethyl-                                                             propylenedioxy)-15-                                                            hydroxy-19,20-dinor-                                                           prostanoic acid                                            379   203           9,9-(2,2-dimethyl-                                                             propylenedioxy)-15-                                                            hydroxy-6,7,19,20-                                                             tetranor-prostanoic                                                            acid                                                       380   205           9,9-(2,2-dimethyl-                                                             propylenedioxy)-15-                                                            hydroxy-5,6,7-trinor-                                                          prostanoic acid                                            381   206           9,9-(2,2-dimethylpro-                                                          pylenedioxy)-15-hydroxy-                                                       6,7-dinor-prostanoic                                                           acid                                                       382   207           9,9-(2,2-dimethylpro-                                                          pylenedioxy)-15-hydroxy-                                                       7a,7b-bishomo-pros-                                                            tanoic acid                                                383   208           9,9-(2,2-dimethylpro-                                                          pylenedioxy)-15-hydroxy-                                                       7-nor-prostanoic acid                                      384   209           9,9-(2,2-dimethylpro-                                                          pylenedioxy)-15-hydroxy-                                                       7a-homo-prostanoic                                                             acid                                                       385   210           9,9-(2,2-dimethyl-                                                             propylenedioxy)-15-                                                            hydroxy-prostanoic                                                             acid                                                       386   212           9,9-(2,2-dimethyl-                                                             propylenedioxy)-15(S)-                                                         hydroxy-prostanoic                                                             acid                                                       387   213           l-9,9-(2,2-dimethyl-                                                           propylenedioxy)-15(S)-                                                         hydroxy-16(R)-methyl-                                                          prostanoic acid                                            388   214           l-9,9-(2,2-dimethyl-                                                           propylenedioxy)-15(S)-                                                         hydroxy-16,16-di-                                                              methyl-prostanoic acid                                     389   215           9,9-(ethylenedithia)-                                                          15-hydroxy-19,20-dinor                                                         prostanoic acid                                            390   216           9,9-(ethylenedithia)-                                                          15-hydroxy-5,6,7,19,-                                                          20-pentanor-prostan-                                                           oic acid                                                   391   217           9,9-(ethylenedithia)-                                                          15-hydroxy-6,7,19,20-                                                          tetranor-prostanoic                                                            acid                                                       392   218           9,9-(ethylenedithia)-                                                          15-hydroxy-7a,7b-                                                              bishomo-19,20-dinor-                                                           prostanoic acid                                            393   219           9,9-(ethylenedithia)-                                                          15-hydroxy-7,19,20-                                                            trinor-prostanoic acid                                     394   220           9,9-(ethylenedithia)-                                                          15-hydroxy-7a-homo-                                                            19,20-dinor-prostanoic                                                         acid                                                       395   225           9,9-(ethylenedithia)-                                                          15-hydroxy-5,6,7-                                                              trinor-prostanoic                                                              acid                                                       396   226           9,9-(ethylenedithia)-                                                          15-hydroxy-6,7-dinor-                                                          prostanoic acid                                            397   227           9,9-(ethylenedithia)-                                                          15-hydroxy-7a,7b-                                                              bishomo-prostanoic                                                             acid                                                       398   228           9,9-(ethylenedithia)-                                                          15-hydroxy-7-nor-                                                              prostanoic acid                                            399   229           9,9-(ethylenedithia)-                                                          15-hydroxy-7a-homo-                                                            prostanoic acid                                            400   230           9,9-(ethylenedithia)-                                                          15-hydroxy-prostanoic                                                          acid                                                       401   235           l-9,9-(ethylenedithia)-                                                        15(R)-hydroxy-pros-                                                            tanoic acid                                                402   236           l-9,9-(ethylenedithia)-                                                        15(S)-hydroxy-pros-                                                            tanoic acid                                                403   237           l-9,9-(ethylenedithia)-                                                        15(S)-hydroxy-16(R)-                                                           methyl-prostanoic acid                                     404   238           l-9,9-(ethylenedithia)-                                                        15(S)-hydroxy-16(S)-                                                           methyl-prostanoic                                                              acid                                                       405   239           l-9,9-(ethylenedithia)-                                                        15(R)-hydroxy-16(S)-                                                           methylprostanoic acid                                      406   240           l-9,9-(ethylenedithia)-                                                        15(R)-hydroxy-16(R)-                                                           methylprostanoic acid                                      407   241           l-9,9-(ethylenedithia)-                                                        15(S)-hydroxy-16,16-                                                           dimethylprostanoic                                                             acid                                                       408   242           l-20-ethyl-9,9-(ethyl-                                                         enedithia)-15(S)-                                                              hydroxy-prostanoic acid                                    409   243           ent-9,9-(ethylenedi-                                                           thia)-15-hydroxy-                                                              prostanoic acid                                            410   244           9,9-(ethyleneoxythia)-                                                         15-hydroxy-19,20-                                                              dinor-prostanoic acid                                      411   245           9,9-(ethyleneoxythia)-                                                         15-hydroxy-5,6,7-                                                              19,20-pentanor-pros-                                                           tanoic acid                                                412   246           9,9-(ethyleneoxythia)-                                                         15-hydroxy-6,7,19,20-                                                          tetranor-prostanoic                                                            acid                                                       413   247           9,9-(ethyleneoxythia)-                                                         15-hydroxy-7a,7b-                                                              bishomo-19,20-dinor-                                                           prostanoic acid                                            414   248           9,9-(ethyleneoxythia)-                                                         15-hydroxy-7,19,20-                                                            trinor-prostanoic acid                                     415   249           9,9-(ethyleneoxythia)-                                                         15-hydroxy-7a-homo-                                                            19,20-dinor-prostanoic                                                         acid                                                       416   254           9,9-(ethyleneoxythia)-                                                         15-hydroxy-5,6,7-                                                              trinor-prostanoic acid                                     417   255           9,9-(ethyleneoxythia)-                                                         15-hydroxy-6,7-dinor-                                                          prostanoic acid                                            418   256           9,9-(ethyleneoxythia)-                                                         15-hydroxy-7a,7b-bis-                                                          homo-prostanoic acid                                       419   257           9,9-(ethyleneoxythia)-                                                         15-hydroxy-7-nor-pros-                                                         tanoic acid                                                420   258           9,9-(ethyleneoxythia)-                                                         15-hydroxy-7a-homo-                                                            prostanoic acid                                            421   259           9,9-(ethyleneoxythia)-                                                         15-hydroxy-prostanoic                                                          acid                                                       422   264           l-9,9-(ethyleneoxythia)-                                                       15(R)-hydroxy-prostan-                                                         oic acid                                                   423   265           l-9,9-(ethyleneoxythia)-                                                       15(S)-hydroxy-pros-                                                            tanoic acid                                                424   266           l-9,9-(ethyleneoxy-                                                            thia)-15(S)-hydroxy-16-                                                        (R)-methyl-prostanoic                                                          acid                                                       425   267           l-9,9-(ethyleneoxy-                                                            thia)-15(S)-hydroxy-                                                           16(S)-methyl-prostan-                                                          oic acid                                                   426   268           l-9,9-(ethyleneoxy-                                                            thia)-15(R)-hydroxy-                                                           16(S)-methyl-pros-                                                             tanoic acid                                                427   269           l-9,9-(ethyleneoxythia)-                                                       15(R)-hydroxy-16(R)-                                                           methyl-prostanoic acid                                     428   270           l-9,9-(ethyleneoxythia)-                                                       15(S)-hydroxy-16,16-                                                           dimethyl-prostanoic                                                            acid                                                       429   271           l-20-ethyl-9,9-(ethyl-                                                         eneoxythia)-15(S)-hy-                                                          droxy-prostanoic acid                                      430   272           ent-9,9-(ethyleneoxy-                                                          thia)-15-hydroxy-pros-                                                         tanoic acid                                                 430A  272A         dl-9,9-(ethylenedioxy-                                                         15-hydroxyprostanoic                                                           acid                                                        430B  272B         dl-15-hydroxy-9,9-(1-                                                          methylethylenedioxy)-                                                          prostanoic acid                                             430C  272C         dl-9,9-(1-chloromethyl-                                                        ethylenedioxy)-15-hy-                                                          droxyprostanoic acid                                        430D  272D         dl-9,9-(1,2-dimethyl-                                                          ethylenedioxy)-15-hy-                                                          droxyprostanoic acid                                        430E  272E         dl-15-hydroxy-9,9-                                                             (propylenedioxy)pros-                                                          tanoic acid                                                 430F  272F         dl-9,9-(ethylenedioxy)-                                                        15-epi-hydroxypros-                                                            tanoic acid                                                 430G  272G         dl-15-epi-hydroxy-9,9-                                                         (1-methylenedi-                                                                oxy)prostanoic acid                                         430H  272H         dl-9,9-(1-chloromethyl-                                                        ethylenedioxy)-15-epi-                                                         hydroxyprostanoic                                                              acid                                                        430I  272I         dl-9,9-(1,2-dimethyl-                                                          ethylenedioxy)-15-                                                             epi-hydroxyprostanoic                                                          acid                                                        430J  272J         dl-15-epi-hydroxy-9,9-                                                         (propylenedioxy)-                                                              prostanoic acid                                            ______________________________________                                    

EXAMPLES 431 - 449

Saponification of the various 15-hydroxy-15-methyl-prostanoate ketals of Table 11 below in the manner of Example 58 above is productive of the corresponding prostanoic acid ketals of the Table.

                  TABLE 11                                                         ______________________________________                                               Starting 15-hy-                                                                droxy-15-methyl-                                                                             Product                                                    Ex-   prostanoate   15-Hydroxy-15-methyl-                                      ample ketals        prostanoic acid ketals                                     ______________________________________                                         431   292           9,9-(ethylenedioxy)-                                                           15-hydroxy-15-methyl-                                                          19,20-dinor-prostan-                                                           oic acid                                                   432   293           9,9-(ethylenedioxy)-                                                           15-hydroxy-15-methyl-                                                          5,6,7,19,20-pentanor-                                                          prostanoic acid                                            433   294           9,9-(ethylenedioxy)-                                                           15-hydroxy-15-methyl-                                                          6,7,19,20-tetranor-                                                            prostanoic acid                                            434   295           15-hydroxy-15-methyl-                                                          9,9-(1-methylethylene-                                                         dioxy)-7a,7b-bishomo-                                                          19,20-dinor-prostanoic                                                         acid                                                       435   296           15-hydroxy-15-methyl-                                                          9,9-(1-methylethylene-                                                         dioxy)-7,19,20-trinor-                                                         prostanoic acid                                            436   297           15-hydroxy-15-methyl-                                                          9,9-(1-methylethylene-                                                         dioxy)-7a-homo-19,20-                                                          dinor-prostanoic acid                                      437   298           9,9-(1,2-dimethylethyl-                                                        enedioxy)-15-hydroxy-                                                          15-methyl-19,20-dinor-                                                         prostanoic acid                                            438   299           15-hydroxy-15-methyl-                                                          9,9-(propylenedioxy)-                                                          19,20-dinor-prostanoic                                                         acid                                                       439   300           15-hydroxy-15-methyl-                                                          9,9-(propylenedioxy)-                                                          19,20-dinor-prostanoic                                                         acid                                                       440   301           15-hydroxy-15-methyl-                                                          9,9-(propylenedioxy)-                                                          19,20-dinor-prostanoic                                                         acid                                                       441   302           9,9-(2,2-dimethylpro-                                                          pylenedioxy)-15-hydroxy-                                                       15-methyl-5,6,7-tri-                                                           nor-prostanoic acid                                        442   303           9,9-(2,2-dimethylpro-                                                          pylenedioxy)-15-hy-                                                            droxy-15-methyl-6,7-di-                                                        nor-prostanoic acid                                        443   304           9,9-(ethylenedithia)-                                                          15-hydroxy-15-methyl-                                                          7a,7b-bishomo-pros-                                                            tanoic acid                                                444   305           9,9-(ethylenedithia)-                                                          15-hydroxy-15-methyl-                                                          7-nor-prostanoic acid                                      445   306           9,9-(ethylenedithia)-                                                          15-hydroxy-15-methyl-                                                          7a-homo-prostanoic                                                             acid                                                       446   307           9,9-(ethyleneoxythia)-                                                         15-hydroxy-15-methyl-                                                          prostanoic acid                                            447   308           9,9-(ethyleneoxythia)-                                                         15-hydroxy-15-methyl-                                                          prostanoic acid                                            448   309           9,9-(ethyleneoxythia)-                                                         15-hydroxy-15-methyl-                                                          prostanoic acid                                            449   310           9,9-(ethyleneoxythia)-                                                         15-hydroxy-15-methyl-                                                          prostanoic acid                                            ______________________________________                                    

EXAMPLE 450 Preparation of l-15(S)-acetoxy-9,9-(ethylenedioxy)prostanoic acid

A solution of 1 g. of l-9,9-(ethylenedioxy)- 15(S)-hydroxy prostanoic acid (Example 324) in 10 ml. of reagent pyridine is treated with 1 ml. of acetic anhydride at ambient temperature for 15 hours. Dilution with water, followed by extraction with chloroform and evaporation to dryness of the chloroform extracts gives an oily material. Treatment of this oil with aqueous methanol at ambient temperature for 18 hours, followed by evaporation affords 950 mg. of product as an oil.

EXAMPLES 451 - 571

Treatment of the various 15-hydroxy-prostanoic acid ketals listed in Table 12 below with the indicated reagent, by the method described in Example 450 above is productive of the esters of the Table.

                                      TABLE 12                                     __________________________________________________________________________          Starting 15-ol                                                            Example                                                                             of Example                                                                              Acylating reagent                                                                         Product                                               __________________________________________________________________________     451  311      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedioxy)-                                                19,20-dinor-prostanoic acid                           452  313      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedioxy)-                                                6,7,19,20-tetranor-prostanoic acid                    453  314      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedioxy)-                                                7a,7b-bishomo-19,20-dinor-prostan-                                             oic acid                                              454  316      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedioxy)-                                                19,20-dinor-prostanoic acid                           455  319      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedioxy)-                                                7a,7b-bishomo-prostanoic acid                         456  320      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedioxy)-7-                                              nor-prostanoic acid                                   457  321      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedioxy)-7a-                                             homo-prostanoic acid                                  458  325      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethylenedioxy)-                                           16(R)-methyl prostanoic acid                          459  329      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethylenedioxy)-                                           16,16-dimethylprostanoic acid                         460  332      Acetic anhydride                                                                          15-acetoxy-9,9-(1-methylethylene-                                              dioxy)-19,20-dinor-prostanoic acid                    461  343      Acetic anhydride                                                                          15-acetoxy-9,9-(1,2-dimethylethyl-                                             enedioxy)-5,6,7-trinor-prostanoic                                              acid                                                  462  350      Acetic anhydride                                                                          15-acetoxy-9,9-(1-chloromethyl-                                                ethylenedioxy)-7-nor-prostanoic                                                acid                                                  463  353      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(1-chloromethyl-                                           enedioxy)-prostanoic acid                             464  356      Acetic anhydride                                                                          l-15(S)-acetoxy-(1-chloromethylene-                                            dioxy)-16,16-dimethylprostanoic acid                  465  361      Acetic anhydride                                                                          15-acetoxy-9,9-(propylenedioxy)-                                               7,19,20-trinor-prostanoic acid                        466  365      Acetic anhydride                                                                          15-acetoxy-9,9-(propylenedioxy)-                                               7a,7b-bishomo-prostanoic acid                         467  370      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(propylene-                                                dioxy)-prostanoic acid                                468  375      Acetic anhydride                                                                          l-15(S)-acetoxy-16,16-dimethyl-                                                9,9-(propylenedioxy)prostanoic acid                   469  381      Acetic anhydride                                                                          15-acetoxy-9,9-(2,2-dimethylpropy-                                             lenedioxy)-6,7-dinor-prostanoic                                                acid                                                  470  391      Acetic anhydride                                                                          15-acetoxy-9,9-(ethylenedithia)-                                               6,7,19,20-tetranor-prostanoic acid                    471  416      Acetic anhydride                                                                          15-acetoxy-9,9-(ethyleneoxythia)-                                              5,6,7-trinor-prostanoic acid                          472  402      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethylenedi-                                               thia)-prostanoic acid                                 473  403      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethylenedithia)-                                          16(R)-methyl-prostanoic acid                          474  407      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethylenedithia)-                                          16,16-dimethyl-prostanoic acid                        475  423      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethyleneoxy-                                              thia)-prostanoic acid                                 476  424      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethyleneoxy-                                              thia)-16(R)-methyl-prostanoic acid                    477  428      Acetic anhydride                                                                          l-15(S)-acetoxy-9,9-(ethyleneoxy-                                              thia)-16,16-dimethylprostanoic acid                   478  313      Propionic anhy-                                                                           9,9-(ethylenedioxy)-15-propionyloxy-                                dride      6,7,19,20-tetranor-prostanoic acid                    479  325      Propionic anhy-                                                                           l-9,9-(ethylenedioxy)-16(R)-methyl-                                 dride      15(S)-propionyloxy-prostanoic acid                    480  333      Propionic anhy-                                                                           9,9-(1-methylethylenedioxy)-15-                                     dride      propionyloxy-5,6,7,19,20-penta-                                                nor-prostanoic acid                                   481  344      Propionic anhy-                                                                           9,9-(1,2-dimethylethylenedioxy)-                                    dride      15-propionyloxy-6,7-dinor-pros-                                                tanoic acid                                           482  349      Propionic anhy-                                                                           9,9-(1-chloromethylethylenedioxy)-                                  dride      15-propionyloxy-7a,7b-bishomo-                                                 prostanoic acid                                       483  353      Propionic anhy-                                                                           l-9,9-(1-chloromethylethylenedioxy)-                                dride      15(S)-propionyloxy-prostanoic acid                    484  356      Propionic anhy-                                                                           l-(1-chloromethylenedioxy)-16,16-                                   dride      dimethyl-15(S)-propionyloxy-                                                   prostanoic acid                                       485  361      Propionic anhy-                                                                           15-propionyloxy-9,9-(propylenedi-                                   dride      oxy)-7,19,20-trinor-prostanoic acid                   486  362      Propionic anhy-                                                                           15-propionyloxy-9,9-(propylenedi-                                   dride      oxy)-7a-homo-19,20-dinor-prostanoic                                            acid                                                  487  363      Propionic anhy-                                                                           15-propionyloxy-9,9-(propylenedi-                                   dride      oxy)-5,6,7-trinor-prostanoic acid                     488  370      Propionic anhy-                                                                           l-15(S)-propionyloxy-9,9-(propyl-                                   dride      enedioxy)-prostanoic acid                             489  375      Propionic anhy-                                                                           l-16,16-dimethyl-15(S)-propionyl-                                   dride      oxy-9,9-(propylenedioxy)prostanoic                                             acid                                                  490  381      Propionic anhy-                                                                           9,9-(2,2-dimethylpropylenedioxy)-                                   dride      15-propionyloxy-6,7-dinor-pros-                                                tanoic acid                                           491  397      Propionic anhy-                                                                           9,9-(ethylenedithia)-15-propionyl-                                  dride      oxy-7a,7b-bishomo-prostanoic acid                     492  402      Propionic anhy-                                                                           l-9,9-(ethylenedithia)-15(S)-pro-                                   dride      pionyloxy-prostanoic acid                             493  403      Propionic anhy-                                                                           l-9,9-(ethylenedithia)-16(R)-                                       dride      methyl-15(S)-propionyloxy-pros-                                                tanoic acid                                           494  407      Propionic anhy-                                                                           l-9,9-(ethylenedithia)-16,16-di-                                    dride      methyl-15(S)-propionyloxy-pros-                                                tanoic acid                                           495  419      Propionic anhy-                                                                           9,9-(ethyleneoxythia)-15-propionyl-                                 dride      oxy-7-nor-prostanoic acid                             496  420      Propionic anhy-                                                                           9,9-(ethyleneoxythia)-15-propionyl-                                 dride      oxy-7a-homo-prostanoic acid                           497  423      Propionic anhy-                                                                           l-9,9-(ethyleneoxythia)-15(S)-pro-                                  dride      pionyloxy-prostanoic acid                             498  424      Propionic anhy-                                                                           l-9,9-(ethyleneoxythia)-16(R)-                                      dride      methyl-15(S)-propionyloxy-pros-                                                tanoic acid                                           499  428      Propionic anhy-                                                                           l-9,9-(ethyleneoxythia)-16,16-di-                                   dride      methyl-15(S)-propionyloxy-prostan-                                             oic acid                                              500  311      Butyric anhy-                                                                             15-butyryloxy-9,9-(ethylenedioxy)-                                  dride      19,20-dinor-prostanoic acid                           501  325      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethylene-                                   dride      dioxy-16(R)-methyl prostanoic acid                    502  329      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethylene-                                   dride      dioxy)-16,16-dimethylprostanoic                                                acid                                                  503  334      Butyric anhy-                                                                             15-butyryloxy-9,9-(1-methylethylene-                                dride      dioxy)-6,7,19,20-tetranor-prostan-                                             oic acid                                              504  342      Butyric anhy-                                                                             15-butyryloxy-9,9-(1,2-dimethyl-                                    dride      ethylenedioxy)-19,20-dinor-pros-                                               tanoic acid                                           505  353      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(1-chloro-                                   dride      methylethylenedioxy)-prostanoic acid                  506  356      Butyric anhy-                                                                             l-15(S)-butyryloxy-(1-chloromethyl-                                 dride      ethylenedioxy)-16,16-dimethylpros-                                             tanoic acid                                           507  364      Butyric anhy-                                                                             15-butyryloxy-9,9-(propylenedioxy)-                                 dride      6,7-dinor-prostanoic acid                             508  370      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(propylene-                                  dride      dioxy)-prostanoic acid                                509  375      Butyric anhy-                                                                             l-15(S)-butyryloxy-16,16-dimethyl-                                  dride      9,9-(propylenedioxy)-prostanoic                                                acid                                                  510  382      Butyric anhy-                                                                             15-butyryloxy-9,9-(2,2-dimethylpro-                                 dride      pylenedioxy)-7a,7b-bishomo-pros-                                               tanoic acid                                           511  394      Butyric anhy-                                                                             15-butyryloxy-9,9-(ethylenedithia)-                                 dride      7a-homo-19,20-dinor-prostanoic                                                 acid                                                  512  402      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethylenedi-                                 dride      thia)-prostanoic acid                                 513  403      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethylenedi-                                 dride      thia)-16(R)-methyl-prostanoic acid                    514  407      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethylenedi-                                 dride      thia)-16,16-dimethyl-prostanoic                                                acid                                                  515  419      Butyric anhy-                                                                             15-butyryloxy-9,9-(ethyleneoxythia)-                                dride      7-nor-prostanoic acid                                 516  423      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethyleneoxy-                                dride      thia)-prostanoic acid                                 517  424      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethyleneoxy-                                dride      thia)-16(R)-methyl-prostanoic acid                    518  428      Butyric anhy-                                                                             l-15(S)-butyryloxy-9,9-(ethylene-                                   dride      oxythia)-16,16-dimethyl-prostanoic                                             acid                                                  519  315      Valeric anhy-                                                                             9,9-(ethylenedioxy)-15-valeryloxy-                                  dride      7,19,20-trinor-prostanoic acid                        520  325      Valeric anhy-                                                                             l-9,9-(ethylenedioxy)-16(R)-methyl-                                 dride      15(S)-valeryloxy-prostanoic acid                      521  329      Valeric anhy-                                                                             l-9,9-(ethylenedioxy)-16,16-di-                                     dride      methyl-15(S)-valeryloxy-prostanoic                                             acid                                                  522  351      Valeric anhy-                                                                             9,9-(1-chloromethylethylenedioxy)-                                  dride      15-valeryloxy-7a-homo-prostanoic                                               acid                                                  523  353      Valeric anhy-                                                                             l-9,9-(1-chloromethylethylenedi-                                    dride      oxy)-15(S)-valeryloxy-prostanoic                                               acid                                                  524  356      Valeric anhy-                                                                             l-(1-chloromethylethylenedioxy)-                                    dride      16,16-dimethyl-15(S)-valeryloxy-                                               prostanoic acid                                       525  366      Valeric anhy-                                                                             9,9-(Propylenedioxy)-15-valeryloxy-                                 dride      7-nor-prostanoic acid                                 526  370      Valeric anhy-                                                                             l-9,9-(propylenedioxy)-15(S)-val-                                   dride      eryloxy-prostanoic acid                               527  375      Valeric anhy-                                                                             l-16,16-dimethyl-9,9-(propylene-                                    dride      dioxy)-15(S)-valeryloxy-prostanoic                                             acid                                                  528  390      Valeric anhy-                                                                             9,9-(Ethylenedithia)-15-valeryloxy-                                 dride      5,6,7,19,20-pentanor-prostanoic                                                acid                                                  529  402      Valeric anhy-                                                                             l-9,9-(ethylenedithia)-15(S)-val-                                   dride      eryloxy-prostanoic acid                               530  403      Valeric anhy-                                                                             l-9,9-(ethylenedithia)-16(R)-methyl-                                dride      15(S)-valeryloxy-prostanoic acid                      531  407      Valeric anhy-                                                                             l-9,9-(ethylenedithia)-16,16-di-                                    dride      methyl-15(S)-valeryloxy-prostanoic                                             acid                                                  532  414      Valeric anhy-                                                                             9,9-(ethyleneoxythia)-15-valeryl-                                   dride      oxy-7,19,20-trinor-prostanoic acid                    533  423      Valeric anhy-                                                                             l-9,9-(ethyleneoxythia)-15(S)-                                      dride      valeryloxy-prostanoic acid                            534  424      Valeric anhy-                                                                             l-9,9-(ethyleneoxythia)-16(R)-                                      dride      methyl-15(S)-valeryloxy-prostanoic                                             acid                                                  535  428      Valeric anhy-                                                                             l-9,9-(ethyleneoxythia)-16,16-di-                                   dride      methyl-15(S)-valeryloxy-prostanoic                                             acid                                                  536  316      Octanoic anhy-                                                                            9,9-(ethylenedioxy)-15-octanoyl-                                    dride      oxy-7a-homo-19,20-dinor-prostanoic                                             acid                                                  537  325      Octanoic anhy-                                                                            l-9,9-(ethylenedioxy)-16(R)-methyl-                                 dride      15(S)-octanoyloxy-prostanoic acid                     538  329      Octanoic anhy-                                                                            l-9,9-(ethylenedioxy)-16,16-di-                                     dride      methyl-15(S)-octanoyloxy-prostanoic                                            acid                                                  539  335      Octanoic anhy-                                                                            9,9-(1-methylethylenedioxy)-15-                                     dride      octanoyloxy-7a,7b-bishomo-19,20-                                               dinor-prostanoic acid                                 540  343      Octanoic anhy-                                                                            9,9-(1,2-dimethylethylenedioxy)-                                    dride      15-octanoyloxy-5,6,7-trinor-                                                   prostanoic acid                                       541  352      Octanoic anhy-                                                                            9,9-(1-chloromethylethylenedioxy)-                                  dride      15-octanoyloxy-prostanoic acid                        542  353      Octanoic anhy-                                                                            l-9,9-(1-chloromethylethylenedi-                                    dride      oxy)-15(S)-octanoyloxy-prostanoic                                              acid                                                  543  356      Octanoic anhy-                                                                            l-(1-chloromethylethylenedioxy)-                                    dride      16,16-dimethyl-15(S)-octanoyloxy-                                              prostanoic acid                                       544  367      Octanoic anhy-                                                                            15-octanoyloxy-9,9-(propylenedi-                                    dride      oxy)-7a-homo-prostanoic acid                          545  370      Octanoic anhy-                                                                            l-15(S)-octanoyloxy-9,9-(propylene-                                 dride      dioxy)-prostanoic acid                                546  375      Octanoic anhy-                                                                            l-16,16-dimethyl-15(S)-octanoyloxy-                                 dride      9,9-(propylenedioxy)-prostanoic                                                acid                                                  547  393      Octanoic anhy-                                                                            9,9-(ethylenedithia)-15-octanoyl-                                   dride      oxy-7,19,20-trinor-prostanoic acid                    548  402      Octanoic anhy-                                                                            l-15(S)-acetoxy-9,9-(ethylenedi-                                    dride      thia)-prostanoic acid                                 549  403      Octanoic anhy-                                                                            l-9,9-(ethylenedithia)-16(R)-methyl-                                dride      15(S)-octanoyloxy-prostanoic acid                     550  407      Octanoic anhy-                                                                            l-9,9-(ethylenedithia)-16,16-di-                                    dride      methyl-15(S)-octanoyloxy-prostanoic                                            acid                                                  551  417      Octanoic anhy-                                                                            9,9-(ethyleneoxythia)-15-octanoyl-                                  dride      oxy-6,7-dinor-prostanoic acid                         552  423      Octanoic anhy-                                                                            l-9,9-(ethyleneoxythia)-15(S)-                                      dride      octanoyloxy-prostanoic acid                           553  424      Octanoic anhy-                                                                            l-9,9-(ethyleneoxythia)-16(R)-                                      dride      methyl-15(S)-octanoyloxy-pros-                                                 tanoic acid                                           554  428      Octanoic anhy-                                                                            l-9,9-(ethyleneoxythia)-16,16-                                      dride      dimethyl-15(S)-octanoyloxy-pros-                                               tanoic acid                                           555  314      Decanoic anhy-                                                                            15-decanoyloxy-9,9-(ethylenedi-                                     dride      oxy)-7a,7b-bishomo-19,20-dinor-                                                prostanoic acid                                       556  325      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      dioxy)-16(R)-methyl-prostanoic acid                   557  329      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      dioxy)-16,16-dimethylprostanoic                                                acid                                                  558  350      Decanoic anhy-                                                                            9,9-(1-chloromethylethylenedioxy)-                                  dride      15-decanoyloxy-7-nor-prostanoic                                                acid                                                  559  353      Decanoic anhy-                                                                            l-9,9-(1-chloromethylethylenedioxy)-                                dride      15(S)-decanoyloxy-prostanoic acid                     560  356      Decanoic anhy-                                                                            l-(1-chloromethylethylenedioxy)-                                    dride      15(S)-16,16-dimethylprostanoic acid                   561  365      Decanoic anhy-                                                                            15-decanoyloxy-9,9-(propylenedioxy)-                                dride      7a,7b-bishomo-prostanoic acid                         562  370      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(propylene-                                 dride      dioxy)-prostanoic acid                                563  375      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-16,16-dimethyl-                                 dride      9,9-(propylenedioxy)prostanoic acid                   564  395      Decanoic anhy-                                                                            15-decanoyloxy-9,9-(ethylenedithia)-                                dride      5,6,7-trinor-prostanoic acid                          565  402      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      dithia)-prostanoic acid                               566  403      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      dithia)-16(R)-methyl-prostanoic acid                  567  407      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      dithia)-16,16-dimethylprostanoic                                               acid                                                  568  415      Decanoic anhy-                                                                            15-decanoyloxy-9,9-(ethyleneoxy-                                    dride      thia)-7a-homo-19,20-dinor-prostanoic                                           acid                                                  569  423      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      oxythia)-prostanoic acid                              570  424      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      oxythia)-16(R)-methyl-prostanoic                                               acid                                                  571  428      Decanoic anhy-                                                                            l-15(S)-decanoyloxy-9,9-(ethylene-                                  dride      oxythia)-16,16-dimethylprostanoic                                              acid                                                  __________________________________________________________________________

EXAMPLES 572 - 734

Treatment of the various prostanoic acid ketals listed in Table 13 below with the indicated diazoalkanes in the manner described in Example 99 is productive of the esters of the Table.

                                      TABLE 13                                     __________________________________________________________________________          Starting acid                                                             Example                                                                             ketal of Example                                                                        Diazoalkane                                                                           Product                                                   __________________________________________________________________________     572  311      Diazomethane                                                                          Methyl 9,9-(ethylenedioxy)-15-                                                 hydrox-19,20-dinor-                                                            prostanoate                                               573  333      Diazomethane                                                                          Methyl 15-hydroxy-9,9-(1-methyl-                                               ethylenedioxy)-5,6,7,19,20-                                                    pentanor-prostanoate                                      574  343      Diazomethane                                                                          Methyl 9,9-(1,2-dimethylethyl-                                                 enedioxy)-15-hydroxy-5,6,7-                                                    trinor-prostanoate                                        575  349      Diazomethane                                                                          Methyl 9,9-(1-chloromethyl-                                                    ethylenedioxy)-15-hydroxy-7a,7b-                                               bishomo-prostanoate                                       576  360      Diazomethane                                                                          Methyl 15-hydroxy-9,9-(propyl-                                                 enedioxy)-7a,7b-bishomo-19,20-                                                 dinor-prostanoate                                         577  394      Diazomethane                                                                          Methyl 9,9-(ethylenedithia)-15-                                                hydroxy-7a-homo-19,20-dinor-                                                   prostanoate                                               578  419      Diazomethane                                                                          Methyl 9,9-(ethyleneoxythia)-15-                                               hydroxy-7-nor-prostanoate                                 579  323      Diazoethane                                                                           Ethyl l-9,9-(ethylenedioxy)-15(R)-                                             hydroxy-prostanoate                                       580  324      Diazoethane                                                                           Ethyl l-9,9-(ethylenedioxy)-15(S)-                                             hydroxy-prostanoate                                       581  326      Diazoethane                                                                           Ethyl l-9,9-(ethylenedioxy)-15(S)-                                             hydroxy-16(S)-methyl-prostanoate                          582  329      Diazoethane                                                                           Ethyl l-9,9-(ethylenedioxy)-15(S)-                                             hydroxy-16,16-dimethyl-pros-                                                   tanoate                                                   583  330      Diazoethane                                                                           Ethyl l-20-ethyl-9,9-(ethylene-                                                dioxy)-15(S)-hydroxy-prostanoate                          584  338      Diazoethane                                                                           Ethyl l-15(S)-hydroxy-9,9-(1-                                                  methylethylenedioxy)-prostanoate                          585  339      Diazoethane                                                                           Ethyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(1-methylethylenedioxy)-                                            prostanoate                                               586  341      Diazoethane                                                                           Ethyl l-15(S)-hydroxy-16,16-di-                                                methyl-9,9-(1-methylethylene-                                                  dioxy)-prostanoate                                        587  345      Diazoethane                                                                           Ethyl l-9,9-(1,2-dimethylethylene-                                             dioxy)-15(S)-hydroxy-prostanoate                          588  346      Diazoethane                                                                           Ethyl l-9,9-(1,2-dimethylethylene-                                             oxy)-15(S)-hydroxy-16(R)-methyl-                                               prostanoate                                               589  348      Diazoethane                                                                           Ethyl l-9,9-(1,2-dimethylethylene-                                             dioxy)-15(S)-hydroxy-16,16-di-                                                 methyl-prostanoate                                        590  353      Diazoethane                                                                           Ethyl l-9,9-(1-chloromethylethyl-                                              enedioxy)-15(S)-hydroxy-prostanoate                       591  354      Diazoethane                                                                           Ethyl l-9,9-(1-chloromethylethyl-                                              enedioxy)-15(S)-hydroxy-16(R)-                                                 methyl-prostanoate                                        592  356      Diazoethane                                                                           Ethyl l-9,9-(1-chloromethylethyl-                                              enedioxy)-15(S)-hydroxy-16,16-                                                 dimethyl-prostanoate                                      593  370      Diazoethane                                                                           Ethyl l-15(S)-hydroxy-9,9-                                                     (propylenedioxy)-prostanoate                              594  371      Diazoethane                                                                           Ethyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(propylenedioxy)-                                                   prostanoate                                               595  375      Diazoethane                                                                           Ethyl l-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(propylenedioxy)-                                                 prostanoate                                               596  402      Diazoethane                                                                           Ethyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-prostanoate                                 597  403      Diazoethane                                                                           Ethyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               598  407      Diazoethane                                                                           Ethyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               599  423      Diazoethane                                                                           Ethyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-prostanoate                                 600  424      Diazoethane                                                                           Ethyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               601  428      Diazoethane                                                                           Ethyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               602  316      Diazobutane                                                                           Butyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-7a-homo-19,20-dinor-                                                   prostanoate                                               603  323      Diazobutane                                                                           Butyl l-9,9-(ethylenedioxy)-15-                                                (R)-hydroxy-prostanoate                                   604  324      Diazobutane                                                                           Butyl l-9,9-(ethylenedioxy)-                                                   15(S)-hydroxy-prostanoate                                 605  326      Diazobutane                                                                           Butyl l-9,9-(ethylenedioxy)-                                                   15(S)-hydroxy-16(S)-methyl-                                                    prostanoate                                               606  329      Diazobutane                                                                           Butyl l-9,9-(ethylenedioxy)-                                                   15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               607  330      Diazobutane                                                                           Butyl l-20-ethyl-9,9-(ethylene-                                                dioxy)-15(S)-hydroxy-prostanoate                          608  338      Diazobutane                                                                           Butyl l-15(S)-hydroxy-9,9-                                                     (1-methylethylenedioxy)-                                                       prostanoate                                               609  339      Diazobutane                                                                           Butyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(1-methylethylene-                                                  dioxy)-prostanoate                                        610  341      Diazobutane                                                                           Butyl l-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(1-methylethylene-                                                dioxy)-prostanoate                                        611  345      Diazobutane                                                                           Butyl l-9,9-(1,2-dimethyl-                                                     ethylenedioxy)-15(S)-hydroxy-                                                  prostanoate                                               612  346      Diazobutane                                                                           Butyl l-9,9-(1,2-dimethyl-                                                     ethylenedioxy)-15(S)-hydroxy-                                                  16(R)-methyl-prostanoate                                  613  348      Diazobutane                                                                           Butyl l-9,9-(1,2-dimethyl-                                                     ethylenedioxy)-15(S)-hydroxy-                                                  16,16-dimethyl-prostanoate                                614  352      Diazobutane                                                                           Butyl 9,9-(1-chloromethyl-                                                     ethylenedioxy)-15-hydroxy-                                                     prostanoate                                               615  353      Diazobutane                                                                           Butyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  prostanoate                                               616  354      Diazobutane                                                                           Butyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16(R)-methyl-prostanoate                                  617  356      Diazobutane                                                                           Butyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16,16-dimethyl-prostanoate                                618  363      Diazobutane                                                                           Butyl 15-hydroxy-9,9-(propylene-                                               dioxy)-5,6,7-trinor-prostanoate                           619  364      Diazobutane                                                                           Butyl 15-hydroxy-9,9-(propyl-                                                  enedioxy)-6,7-dinor-prostanoate                           620  370      Diazobutane                                                                           Butyl 1-15(S)-hydroxy-9,9-                                                     propylenedioxy)-prostanoate                               621  371      Diazobutane                                                                           Butyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(propylenedioxy)-                                                   prostanoate                                               622  375      Diazobutane                                                                           Butyl l-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(propylene-                                                       dioxy)-prostanoate                                        623  382      Diazobutane                                                                           Butyl 9,9-(2,2-dimethyl-                                                       (propylenedioxy)-15-hydroxy-                                                   7a,7b-bishomo-prostanoate                                 624  390      Diazobutane                                                                           Butyl 9,9-(ethylenedithia)-                                                    15-hydroxy-5,6,7,19,20-                                                        pentanor-prostanoate                                      625  397      Diazobutane                                                                           Butyl 9,9-(ethylenedithia)-                                                    15-hydroxy-7a,7b-bishomo-                                                      prostanoate                                               626  402      Diazobutane                                                                           Butyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-prostanoate                                 627  403      Diazobutane                                                                           Butyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               628  407      Diazobutane                                                                           Butyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               629  415      Diazobutane                                                                           Butyl 9,9-(ethyleneoxythia)-                                                   15-hydroxy-7a-homo-19,20-                                                      dinor-prostanoate                                         630  420      Diazobutane                                                                           Butyl 9,9-(ethyleneoxythia)-                                                   15-hydroxy-7a-homo-prostanoate                            631  423      Diazobutane                                                                           Butyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-prostanoate                                 632  424      Diazobutane                                                                           Butyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               633  428      Diazobutane                                                                           Butyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               634  320      Diazohexane                                                                           Hexyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-7-nor-prostanoate                                 635  323      Diazohexane                                                                           Hexyl l-9,9-(ethylenedioxy)-15-                                                (R)-hydroxy-prostanoate                                   636  324      Diazohexane                                                                           Hexyl l-9,9-(ethylenedioxy)-15-                                                (S)-hydroxy-prostanoate                                   637  326      Diazohexane                                                                           Hexyl l-9,9-(ethylenedioxy)-15-                                                (S)-hydroxy-16(S)-methyl-                                                      prostanoate                                               638  329      Diazohexane                                                                           Hexyl l-9,9-(ethylenedioxy)-15-                                                (S)-hydroxy-16,16-dimethyl-                                                    prostanoate                                               639  330      Diazohexane                                                                           Hexyl l-20-ethyl-9,9-(ethylene-                                                dioxy)-15(S)-hydroxy-prostanoate                          640  337      Diazohexane                                                                           Hexyl 15-hydroxy-9,9-(1-methyl-                                                ethylenedioxy)-7a-homo-19,20-                                                  dinor-prostanoate                                         641  338      Diazohexane                                                                           Hexyl l-15(S)-hydroxy-9,9-(1-                                                  methylethylenedioxy)-prostanoate                          642  339      Diazohexane                                                                           Hexyl 1-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(1-methylethylene-                                                  dioxy)-prostanoate                                        643  341      Diazohexane                                                                           Hexyl l-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(1-methylethylene-                                                dioxy)-prostanoate                                        644  344      Diazohexane                                                                           Hexyl 9,9-(1,2-dimethylethyl-                                                  enedioxy)-15-hydroxy-6,7-dinor-                                                prostanoate                                               645  345      Diazohexane                                                                           Hexyl l-9,9-(1,2-dimethylethyl-                                                enedioxy)-15(S)-hydroxy-pros-                                                  tanoate                                                   646  346      Diazohexane                                                                           Hexyl l-9,9-(1,2-dimethylethyl-                                                enedioxy)-15(S)-hydroxy-16(R)-                                                 methyl-prostanoate                                        647  348      Diazohexane                                                                           Hexyl l-9,9-(1,2-dimethylethyl-                                                enedioxy)-15(S)-hydroxy-16,16-                                                 dimethyl-prostanoate                                      648  351      Diazohexane                                                                           Hexyl 9,9-(1-chloromethylethyl-                                                enedioxy)-15-hydroxy-7a-homo-                                                  prostanoate                                               649  353      Diazohexane                                                                           Hexyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  prostanoate                                               650  354      Diazohexane                                                                           Hexyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16(R)-methyl-prostanoate                                  651  356      Diazohexane                                                                           Hexyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16,16-dimethyl-prostanoate                                652  361      Diazohexane                                                                           Hexyl 15-hydroxy-9,9-(propyl-                                                  enedioxy)-7,19,20-trinor-                                                      prostanoate                                               653  370      Diazohexane                                                                           Hexyl l-15(S)-hydroxy-9,9-(pro-                                                pylenedioxy)-prostanoate                                  654  371      Diazohexane                                                                           Hexyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(propylenedioxy)-                                                   prostanoate                                               655  375      Diazohexane                                                                           Hexyl l-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(propylenedioxy)-                                                 prostanoate                                               656  389      Diazohexane                                                                           Hexyl 9,9-(ethylenedithia)-15-                                                 hydroxy-19,20-dinor-prostanoate                           657  402      Diazohexane                                                                           Hexyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-prostanoate                                 658  403      Diazohexane                                                                           Hexyl 9,9-(ethylenedithia)-                                                    15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               659  407      Diazohexane                                                                           Hexyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               660  418      Diazohexane                                                                           Hexyl 9,9-(ethyleneoxythia)-15-                                                hydroxy-7a,7b-bishomo-prostanoate                         661  423      Diazohexane                                                                           Hexyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-prostanoate                                 662  424      Diazohexane                                                                           Hexyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               663  428      Diazohexane                                                                           Hexyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               664  311      Diazooctane                                                                           Octyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-19,20-dinor-prostanoate                           665  313      Diazooctane                                                                           Octyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-6,7,19,20-tetranor-                                                    prostanoate                                               666  316      Diazooctane                                                                           Octyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-7a-homo-19,20-dinor-                                                   prostanoate                                               667  319      Diazooctane                                                                           Octyl 9,9-(ethylenedioxy)-7a,-                                                 7b-bishomo-prostanoate                                    668  323      Diazooctane                                                                           Octyl l-9,9-(ethylenedioxy)-15-                                                (R)-hydroxy-prostanoate                                   669  324      Diazooctane                                                                           Octyl l-9,9-(ethylenedioxy)-15(S)-                                             hydroxy-prostanoate                                       670  326      Diazooctane                                                                           Octyl l-9,9-(ethylenedioxy)-15(S)-                                             hydroxy-16(S)-methyl-prostanoate                          671  329      Diazooctane                                                                           Octyl l-9,9-(ethylenedioxy)-15(S)-                                             hydroxy-16,16-dimethyl-prostanoate                        672  330      Diazooctane                                                                           Octyl l-20-ethyl-9,9-(ethylene-                                                dioxy)-15(S)-hydroxy-prostanoate                          673  338      Diazooctane                                                                           Octyl l-15(S)-hydroxy-9,9-(1-                                                  methylethylenedioxy)prostanoate                           674  339      Diazooctane                                                                           Octyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(1-methylethylenedioxy)-                                            prostanoate                                               675  341      Diazooctane                                                                           Octyl l-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(1-methylethylene-                                                dioxy)-prostanoate                                        676  345      Diazooctane                                                                           Octyl l-9,9-(1,2-dimethylethyl-                                                enedioxy)-15(S)-hydroxy-prostanoate                       677  346      Diazooctane                                                                           Octyl l-9,9-(1,2-dimethylethyl-                                                enedioxy)-15(S)-hydroxy-16(R)-                                                 methyl-prostanoate                                        678  348      Diazooctane                                                                           Octyl l-9,9-(1,2-dimethylethyl-                                                enedioxy)-15(S)-hydroxy-16,16-                                                 dimethyl-prostanoate                                      679  350      Diazooctane                                                                           Octyl 9,9-(1-chloromethyl-                                                     ethylenedioxy)-15-hydroxy-7-                                                   nor-prostanoate                                           680  353      Diazooctane                                                                           Octyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  prostanoate                                               681  354      Diazooctane                                                                           Octyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16(R)-methyl-prostanoate                                  682  356      Diazooctane                                                                           Octyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16,16-dimethyl-prostanoate                                683  361      Diazooctane                                                                           Octyl 15-hydroxy-9,9-(propyl-                                                  enedioxy)-7,19,20-trinor-pros-                                                 tanoate                                                   684  365      Diazooctane                                                                           Octyl 15-hydroxy-9,9-(propylene-                                               dioxy)-7a,7b-bishomo-pros-                                                     tanoate                                                   685  370      Diazooctane                                                                           Octyl l-15(S)-hydroxy-9,9-(propyl-                                             enedioxy)-prostanoate                                     686  371      Diazooctane                                                                           Octyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(propylenedioxy)-                                                   prostanoate                                               687  375      Diazooctane                                                                           Octyl l-15(S)-hydroxy-16,16-di-                                                methyl-9,9-(propylenedioxy)-                                                   prostanoate                                               688  394      Diazooctane                                                                           Octyl 9,9-(ethylenedithia)-15-                                                 hydroxy-7a-homo-19,20-dinor-                                                   prostanoate                                               689  397      Diazooctane                                                                           Octyl 9,9-(ethylenedithia)-15-                                                 hydroxy-7a,7b-bishomo-prostanoate                         690  402      Diazooctane                                                                           Octyl l-9,9-(ethylenedithia)-15-                                               (S)-hydroxy-prostanoate                                   691  404      Diazooctane                                                                           Octyl l-9,9-(ethylenedithia)-15-                                               (S)-hydroxy-16(S)-methyl-pros-                                                 tanoate                                                   692  407      Diazooctane                                                                           Octyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               693  412      Diazooctane                                                                           Octyl 9,9-(ethyleneoxythia)-                                                   15-hydroxy-6,7,19,20-tetra-                                                    nor-prostanoate                                           694  419      Diazooctane                                                                           Octyl 9,9-(ethyleneoxythia)-                                                   7-nor-prostanoate                                         695  423      Diazooctane                                                                           Octyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-prostanoate                                 696  424      Diazooctane                                                                           Octyl 9,9-(ethyleneoxythia)-                                                   15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               697  428      Diazooctane                                                                           Octyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               698  313      Diazodecane                                                                           Decyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-6,7,19,20-tetranor-                                                    prostanoate                                               699  316      Diazodecane                                                                           Decyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-7a-homo-19,20-dinor-                                                   prostanoate                                               700  319      Diazodecane                                                                           Decyl 9,9-(ethylenedioxy)-15-                                                  hydroxy-7a,7b-bishomo-pros-                                                    tanoate                                                   701  323      Diazodecane                                                                           Decyl l-9,9-(ethylenedioxy)-                                                   15(R)-hydroxy-prostanoate                                 702  324      Diazodecane                                                                           Decyl l-9,9-(ethylenedioxy)-                                                   15(S)-hydroxy-prostanoate                                 703  326      Diazodecane                                                                           Decyl l-9,9-(ethylenedioxy)-15-                                                (S)-hydroxy-16(S)-methyl-                                                      prostanoate                                               704  329      Diazodecane                                                                           Decyl l-9,9-(ethylenedioxy)-                                                   15(S)-hydroxy-16,16-di-                                                        methyl-prostanoate                                        705  330      Diazodecane                                                                           Decyl l-20-ethyl-9,9-(ethyl-                                                   enedioxy)-15(S)-hydroxy-                                                       prostanoate                                               706  338      Diazodecane                                                                           Decyl l-15(S)-hydroxy-9,9-                                                     (1-methylethylenedioxy)-                                                       prostanoate                                               707  339      Diazodecane                                                                           Decyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(1-methylethyl-                                                     enedioxy)-prostanoate                                     708  341      Diazodecane                                                                           Decyl 1-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(1-methylethyl-                                                   enedioxy)-prostanoate                                     709  345      Diazodecane                                                                           Decyl l-9,9-(1,2-dimethyl-                                                     ethylenedioxy)-15(S)-hydroxy-                                                  prostanoate                                               710  346      Diazodecane                                                                           Decyl l-9,9-(1,2-dimethyl-                                                     ethylenedioxy)-15(S)-hydroxy-                                                  16(R)-methyl-prostanoate                                  711  348      Diazodecane                                                                           Decyl l-9,9-(1,2-dimethyl-                                                     ethylenedioxy)-15(S)-hydroxy-                                                  16,16-dimethyl-prostanoate                                712  353      Diazodecane                                                                           Decyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  prostanoate                                               713  354      Diazodecane                                                                           Decyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16(R)-methyl-prostanoate                                  714  356      Diazodecane                                                                           Decyl l-9,9-(1-chloromethyl-                                                   ethylenedioxy)-15(S)-hydroxy-                                                  16,16-dimethyl-prostanoate                                715  359      Diazodecane                                                                           Decyl 15-hydroxy-9,9-(propyl-                                                  enedioxy)-6,7,19,20-tetranor-                                                  prostanoate                                               716  366      Diazodecane                                                                           Decyl 15-hydroxy-9,9-(propyl-                                                  enedioxy)-7-nor-prostanoate                               717  367      Diazodecane                                                                           Decyl 15-hydroxy-9,9-(propyl-                                                  enedioxy)-7a-homo-prostanoate                             718  370      Diazodecane                                                                           Decyl l-15(S)-hydroxy-(9,9-                                                    propylenedioxy)-prostanoate                               719  371      Diazodecane                                                                           Decyl l-15(S)-hydroxy-16(R)-                                                   methyl-9,9-(propylenedioxy)-                                                   prostanoate                                               720  375      Diazodecane                                                                           Decyl l-15(S)-hydroxy-16,16-                                                   dimethyl-9,9-(propylenedioxy)-                                                 prostanoate                                               721  381      Diazodecane                                                                           Decyl 9,9-(2,2-dimethylpropyl-                                                 enedioxy)-15-hydroxy-6,7-dinor-                                                prostanoate                                               722  390      Diazodecane                                                                           Decyl 9,9-(ethylenedithia)-15-                                                 hydroxy-5,6,7,19,20-pentanor-                                                  prostanoate                                               723  393      Diazodecane                                                                           Decyl 9,9-(ethylenedithia)-                                                    15-hydroxy-7,19,20-trinor-                                                     prostanoate                                               724  396      Diazodecane                                                                           Decyl 9,9-(ethylenedithia)-                                                    15-hydroxy-6,7-dinor-pros-                                                     tanoate                                                   725  399      Diazodecane                                                                           Decyl 9,9-(ethylenedithia)-                                                    15-hydroxy-7a-homo-prostanoate                            726  402      Diazodecane                                                                           Decyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-prostanoate                                 727  403      Diazodecane                                                                           Decyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               728  407      Diazodecane                                                                           Decyl l-9,9-(ethylenedithia)-                                                  15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               729  410      Diazodecane                                                                           Decyl 9,9-(ethyleneoxythia)-                                                   15-hydroxy-19,20-dinor-pros-                                                   tanoate                                                   730  413      Diazodecane                                                                           Decyl 9,9-(ethyleneoxythia)-                                                   15-hydroxy-7a,7b-bis-homo-                                                     19,20-dinor-prostanoate                                   731  418      Diazodecane                                                                           Decyl 9,9-(ethyleneoxythia)-                                                   15-hydroxy-7a,7b-bishomo-                                                      prostanoate                                               732  423      Diazodecane                                                                           Decyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-prostanoate                                 733  424      Diazodecane                                                                           Decyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16(R)-methyl-                                                    prostanoate                                               734  428      Diazodecane                                                                           Decyl l-9,9-(ethyleneoxythia)-                                                 15(S)-hydroxy-16,16-dimethyl-                                                  prostanoate                                               __________________________________________________________________________

EXAMPLE 735 Preparation of 1-methyl 9,9-(ethylenedioxy)-15-oxo-prostanoate

To a mixture of 14.5 g. of chromium trioxide-pyridine complex in 110 ml. of dry methylene chloride is added with stirring 4.82 g. of 1-methyl 9,9-(ethylenedioxy)-15(S)-hydroxy-prostanoate (Example 134) in 17 ml. of methylene chloride. The resulting dark brown mixture is stirred at ambient temperature for 18 hours. The mixture is filtered and the mother liquor is taken to dryness. The residue is taken up in ether and washed successively with ice cold 5% sodium hydroxide, saturated sodium chloride solution, 30% sodium phosphate monobasic solution and water dried with anhydrous sodium sulfate and evaporated to dryness under reduced pressure to afford 4.17 g. (98%) of product as an oil; λ max 5.71, 5.82μ (carbonyl groups).

EXAMPLE 736 Preparation of 1-methyl-9,9-(ethylenedioxy)-15-hydroxy-15-methyl-prostanoate

To a Grignard solution prepared from 363 mg. (2 equivalents) of magnesium and 2.16 g. (2 equivalents) of methyl iodide in 10 ml. of ether under argon atmosphere is added dropwise a solution of 3 g. of 1-methyl 9,9-(ethylenedioxy)-15-oxo-prostanoate (Example 735) in 15 ml. of ether and the resulting mixture is stirred at ambient temperature for 18 hours. Saturated ammonium chloride (20 ml.) is added followed by 15 ml. of water and 50 ml. of ether. The ethereal solution is washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate and taken to dryness to give 3.04 g. of viscous oil. This material is chromatographed on 75 g. of Florisil. The product is eluted with benzene to give 880 mg. of product. Further elution of the column with 10% ether in benzene gives 1.3 g. of 1-1,1-dimethyl-15-methyl-15-hydroxy-9,9-ethylenedioxy-prostanyl alcohol.

EXAMPLE 737 Preparation of 1-9,9-(ethylenedioxy)-15-hydroxy-15-methyl-prostanoic acid

Treatment of 1-methyl 9,9-(ethylenedioxy)-15-hydroxy-15-methyl-prostanoate (Example 736) with potassium hydroxide in the manner of Example 58 is productive of the subject compound.

EXAMPLES 738 - 744

Treatment of the various hydroxyprostanoate ketals of Table 14 below with chromium trioxide-pyridine complex in the manner of Example 735 above is productive of the corresponding 15-oxoprostanoate ketals of the Table.

                  TABLE 14                                                         ______________________________________                                                Starting 15-hy-                                                                              Product                                                   Ex-    droxyprostanoate                                                                             15-oxoprostanoate                                         ample  ketals of Example                                                                            ketals                                                    ______________________________________                                         738    140           methyl l-20-ethyl-9,9-                                                         (ethylenedioxy)-15-                                                            oxoprostanoate                                            739    141           ent-methyl 9,9-(ethyl-                                                         enedioxy)-15-oxopros-                                                          tanoate                                                   740    148           methyl l-9,9-(1-methyl-                                                        ethylenedioxy)-15-oxo-                                                         prostanoate                                               741    194           methyl l-15-oxo-9,9-                                                           (propylenedioxy)-                                                              prostanoate                                               742    200           methyl l-20-ethyl-15-                                                          oxo-9,9-(propylene-                                                            dioxy)-prostanoate                                        743    201           ent-methyl 15-oxo-9,9-                                                         (propylenedioxy)-                                                              prostanoate                                               744    212           methyl l-9,9-(2,2-di-                                                          methylpropylenedioxy)-                                                         15-oxoprostanoate                                         ______________________________________                                    

EXAMPLES 745-751

Treatment of the various 15-oxoprostanoate ketals of Table 15 below with methyl magnesium iodide in the manner of Example 736 is productive of the corresponding 15-hydroxy-15-methyl prostanoate ketals of the table. The products are obtained as a mixture of the 15(S) and 15(R) components.

                  TABLE 15                                                         ______________________________________                                                Starting 15-oxo-                                                                             Product                                                   Ex-    prostanoate   15-hydroxy-15-methyl-                                     ample  ketals of Example                                                                            prostanoate ketals                                        ______________________________________                                         745    738           methyl l-20-ethyl-9,9-                                                         (ethylenedioxy)-15-                                                            hydroxy-15-methyl-                                                             prostanoate                                               746    739           ent-methyl 9,9-(ethyl-                                                         enedioxy)-15-hydroxy-                                                          15-methylprostanoate                                      747    740           methyl l-15-hydroxy-                                                           15-methyl-9,9-(1-                                                              methylethylenedioxy)-                                                          prostanoate                                               748    741           methyl l-15-hydroxy-                                                           15-methyl-9,9-(pro-                                                            pylenedioxy)prostanoate                                   749    742           methyl l-20-ethyl-15-                                                          hydroxy-15-methyl-                                                             9,9-(propylenedioxy)-                                                          prostanoate                                               750    743           ent-methyl 15-hydroxy-                                                         15-methyl-9,9-(pro-                                                            pylenedioxy)prostanoate                                   751    744           methyl l-9,9-(2,2-di-                                                          methylpropylenedioxy)-                                                         15-hydroxy-15-methyl-                                                          prostanoate                                               ______________________________________                                    

EXAMPLES 752-759

Saponification of the various 15-hydroxy-15-methyl-prostanoate ketals of Table 16 below in the manner of Example 58 is productive of the corresponding 15-hydroxy-15-methyl-prostanoic acid ketals of the Table.

                  TABLE 16                                                         ______________________________________                                                Starting 15-hy-                                                                droxy-15-methyl-                                                                             Product                                                   Ex-    prostanoate   15-hydroxy-15-methyl-                                     ample  ketals of Example                                                                            prostanoic acid ketal                                     ______________________________________                                         752    736           l-9,9-(ethylenedioxy)-                                                         15-hydroxy-15-methyl-                                                          prostanoic acid                                           753    745           l-20-ethyl-9,9-(ethyl-                                                         enedioxy)-15-hydroxy-                                                          15-methylprostanoic                                                            acid                                                      754    746           ent-9,9-(ethylenedi-                                                           oxy)-15-hydroxy-15-                                                            methylprostanoic acid                                     755    747           l-15-hydroxy-15-methyl-                                                        9,9-(1-methylethyl-                                                            enedioxy)prostanoic                                                            acid                                                      756    748           l-15-hydroxy-15-methyl-                                                        9,9-(propylenedioxy)-                                                          prostanoic acid                                           757    749           l-20-ethyl-15-hydroxy-                                                         15-methyl-9,9-(pro-                                                            pylenedioxy)prostanoic                                                         acid                                                      758    750           ent-15-hydroxy-15-                                                             methyl-9,9-(propylene-                                                         dioxy)prostanoic acid                                     759    751           l-9,9-(2,2-dimethylpro-                                                        pylenedioxy)-15-hy-                                                            droxy-15-methylpros-                                                           tanoic acid                                               ______________________________________                                    

EXAMPLES 760-763

In the manner described in Example 99, treatment of the various prostatrienoic acids listed in Table 17 below with ethereal diazomethane is productive of the corresponding methyl prostatrienoates of the Table.

                                      TABLE 17                                     __________________________________________________________________________                           Product                                                  Example                                                                             Starting prostatrienoic acids                                                                   Methyl prostatrienoates                                  __________________________________________________________________________     760  l-16-fluoro-15(S)-hydroxy-                                                                      l-methyl 16-fluoro-15(S)-hydroxy-9-                           9-oxo-5-cis,10,13-trans-                                                                        oxo-5-cis,10,13-trans-prostatrienoate                         prostatrienoic acid.sup.1                                                 761  l-16-fluoro-15(R)-hydroxy-                                                                      l-methyl 16-fluoro-15(R)-hydroxy-9-                           9-oxo-5-cis,10,13-trans-                                                                        oxo-5-cis,10,13-trans-prostatrienoate                         prostatrienoic acid.sup.1                                                 762  l-16,16-difluoro-15(S)-hy-                                                                      l-methyl 16,16-difluoro-15(S)-hydroxy-                        droxy-9-oxo-5-cis,10,13-                                                                        9-oxo-5-cis,10,13-trans-prostatrienoate                       trans-prostatrienoic acid.sup.1                                           763  l-16,16-difluoro-15(R)-hy-                                                                      l-methyl 16,16-difluoro-15(R)-hydroxy-                        droxy-9-oxo-5-cis,10,13-                                                                        9-oxo-5-cis,10,13-trans-prostatrienoate                       trans-prostatrienoic acid.sup.1                                           __________________________________________________________________________      .sup.1 Netherlands Patent No. 7,305,817.                                 

EXAMPLES 764-767

Hydrogenation of the various prostatrienoic acid methyl esters in Table 18 below using 5% rhodium-on-carbon catalyst in ethyl acetate all in the manner described in Example 52 above is productive of the prostanoic acid methyl esters of the Table.

                  TABLE 18                                                         ______________________________________                                                Starting prosta-                                                               trienoic acid Product                                                   Ex-    methyl esters of                                                                             Prostanoic acid methyl                                    ample  Example       esters                                                    ______________________________________                                         764    760           l-methyl 16-fluoro-                                                            15(S)-hydroxy-9-oxo-                                                           prostanoate                                               765    761           l-methyl 16-fluoro-                                                            15(R)-hydroxy-9-oxo-                                                           prostanoate                                               766    762           l-methyl 16,16-difluoro-                                                       15(S)-hydroxy-9-oxo-                                                           prostanoate                                               767    763           l-methyl 16,16-difluoro-                                                       15(R)-hydroxy-9-oxo-                                                           prostanoate                                               ______________________________________                                    

EXAMPLES 768-787

Treatment of the various 9-oxoprostanoates listed in Table 19 below with the indicated reagent, by the method described in Example 55 above, is productive of the ketals of the Table.

                                      TABLE 19                                     __________________________________________________________________________          Starting 9-oxo-                                                                prostanoates of    Product                                                Example                                                                             Example  Ketalizing reagent                                                                       Prostanoate ketals                                     __________________________________________________________________________     768  764      ethylene glycol                                                                          l-methyl 9,9-(ethylenedioxy)-16-fluoro-                                        15(S)-hydroxyprostanoate                               769  764      1,2-propanediol                                                                          l-methyl 16-fluoro-15(S)-hydroxy-9,9-                                          (1-methylethylenedioxy)prostanoate                     770  764      1-chloro-2,3-                                                                            l-methyl 9,9-(1-chloromethylethylene-                                propanediol                                                                              dioxy)-16-fluoro-15(S)-hydroxyprostanoate              771  764      2,3-butanediol                                                                           l-methyl 9,9-(1,2-dimethylethylenedioxy)-                                      16-fluoro-15(S)-hydroxyprostanoate                     772  764      1,3-propanediol                                                                          l-methyl 16-fluoro-15(S)-hydroxy-9,9-                                          (propylenedioxy)prostanoate                            773  765      ethylene glycol                                                                          l-methyl 9,9-(ethylenedioxy)-16-fluoro-                                        15(R)-hydroxyprostanoate                               774  765      1,2-propanediol                                                                          l-methyl 16-fluoro-15(R)-hydroxy-9,9-                                          (1-methylethylenedioxy)prostanoate                     775  765      1-chloro-2,3-                                                                            l-methyl 9,9-(1-chloromethylethylene-                                propanediol                                                                              dioxy)-16-fluoro-15(R)-hydroxyprostanoate              776  765      2,3-butanediol                                                                           l-methyl 9,9-(1,2-dimethylethylenedioxy)-                                      16-fluoro-15(R)-hydroxyprostanoate                     777  765      1,3-propanediol                                                                          l-methyl 16-fluoro-15(R)-hydroxy-9,9-                                          (propylenedioxy)prostanoate                            778  766      ethylene glycol                                                                          l-methyl 9,9-(ethylenedioxy)-16,16-di-                                         fluoro-15(S)-hydroxyprostanoate                        779  766      1,2-propanediol                                                                          l-methyl 16,16-difluoro-15(S)-hydroxy-                                         9,9-(1-methylethylenedioxy)prostanoate                 780  766      1-chloro-2,3-                                                                            l-methyl 9,9-(1-chloromethylethylenedi-                              propanediol                                                                              oxy)-16,16-difluoro-15(S)-hydroxyprostanoate           781  766      2,3-butanediol                                                                           l-methyl 9,9-(1,2-dimethylethylenedioxy)-                                      16,16-difluoro-15(S)-hydroxyprostanoate                782  766      1,3-propanediol                                                                          l-methyl 16,16-difluoro-15(S)-hydroxy-9,9-                                     (propylenedioxy)prostanoate                            783  767      ethylene glycol                                                                          l-methyl 9,9-(ethylenedioxy)-16,16-difluoro-                                   15(R)-hydroxyprostanoate                               784  767      1,2-propanediol                                                                          l-methyl 16,16-difluoro-15(R)-hydroxy-9,9-                                     (1-methylethylenedioxy)prostanoate                     785  767      1-chloropropane-                                                                         l-methyl-9,9-(1-chloromethylethylenedioxy)-                          diol      16,16-difluoro-15(R)-hydroxyprostanoate                786  767      2,3-butanediol                                                                           l-methyl 9,9-(1,2-dimethylethylenedioxy)-                                      16,16-difluoro-15(R)-hydroxyprostanoate                787  767      1,3-propanediol                                                                          l-methyl 16,16-difluoro-15(R)-hydroxy-9,9-                                     (propylenedioxy)prostanoate                            __________________________________________________________________________

EXAMPLES 788-807

Saponification of the various prostanoate ketals of Table 20 below in the manner of Example 58 above is productive of the prostanoic acid ketals of the Table.

                                      TABLE 20                                     __________________________________________________________________________          Starting Prostanoate                                                      Example                                                                             ketals of Example                                                                          Product Prostanoic Acid Ketals                                __________________________________________________________________________     788  768         l-9,9-(ethylenedioxy)-16-fluoro-15(S)-hydroxy                                  prostanoic                                                                     acid                                                          789  769         l-16-fluoro-15(S)-hydroxy-9,9-(1-methylethylenedioxy)-                         prostanoic acid                                               790  770         l-9,9-(1-chloromethylethylenedioxy)-16-fluoro-15-(S)-                          hydroxy-prostanoic acid                                       791  771         l-9,9-(1,2-dimethylethylenedioxy)-16-fluoro-15(S)-hydroxy                      5                                                                              prostanoic acid                                               792  772         l-16-fluoro-15(S)-hydroxy-9,9-(propylenedioxy)prostanoic                       acid                                                          793  773         l-9,9-(ethylenedioxy)-16-fluoro-15(R)-hydroxy                                  prostanoic                                                                     acid                                                          794  774         l-16-fluoro-15(R)-hydroxy-9,9-(1-methylethylenedioxy)-                         prostanoic acid                                               795  775         l-9,9-(1-chloromethylethylenedioxy)-16-fluoro-15(R)-                           hydroxy prostanoic acid                                       796  776         l-9,9-(1,2-dimethylethylenedioxy-16-fluoro-15(R)-hydroxy-                      prostanoic acid                                               797  777         l-16-fluoro-15(R)-hydroxy-9,9-(propylenedioxy)prostanoic                       acid                                                          798  778         l-9,9-(ethylenedioxy)-16,16-difluoro-15(S)-hydroxy                             prostanoic                                                                     acid                                                          799  779         l-16,16-difluoro-15(S)-hydroxy-9,9-(1-methylethylenedioxy                      )-                                                                             prostanoic acid                                               800  780         l-9,9-(1-chloromethylethylenedioxy)-16,16-difluoro-15(S)-                      hydroxy prostanoic acid                                       801  781         l-9,9-(1,2-dimethylethylenedioxy)-16,16-difluoro-15(S)-                        hydroxy prostanoic acid                                       802  782         l-16,16-difluoro-15(S)-hydroxy-9,9-(propylenedioxy)prosta                      noic                                                                           acid                                                          803  783         l-9,9-(ethylenedioxy)-16,16-difluoro-15(R)-hydroxy                             prostanoic                                                                     acid                                                          804  784         l-16,16-difluoro-15(R)-hydroxy-9,9-(1-methylethylenedioxy                      )-                                                                             prostanoic acid                                               805  785         l-9,9-(1-chloromethylethylenedioxy)-16,16-difluoro-15(R)-                      hydroxy prostanoic acid                                       806  786         l-9,9-(1,2-dimethylethylenedioxy)-16,16-difluoro-15(R)-                        hydroxy prostanoic acid                                       807  787         l-16,16-difluoro-15(R)-hydroxy-9,9-(propylenedioxy)prosta                      noic                                                                           acid                                                          __________________________________________________________________________

EXAMPLES 808-814

Treatment of the various prostatrienoic acids listed in Table 21 below with the indicated diazoalkanes, in the manner described in Example 99 above is productive of the esters of the Table.

                                      TABLE 21                                     __________________________________________________________________________     Example                                                                             Starting Prostatrienoic Acid                                                                    Diazoalkane Product                                      __________________________________________________________________________     808  l-16-fluoro-15(S)-hydroxy-9-                                                                    diazobutane                                                                           l-butyl 16-fluoro-15(S)-                               oxo-5-cis,10,13-trans-pro-                                                                             hydroxy-9-oxo-5-cis,10,13-                             statrienoic acid.sup.1  trans-prostatrienoate                             809  l-16-fluoro-15(S)-hydroxy-9-                                                                    diazodecane                                                                           l-decyl 16-fluoro-15(S)-                               oxo-5-cis,10,13-trans-pro-                                                                             hydroxy-9-oxo-5-cis,10,13-                             statrienoic acid        trans-prostatrienoate                             810  l-16-fluoro-15(R)-hydroxy-9-                                                                    diazopentane                                                                          l-pentyl 16-fluoro-15(R)-                              oxo-5-cis,10,13-trans-pro                                                                              hydroxy-9-oxo-5-cis,10,13-                             statrienoic acid.sup.1  trans-prostatrienoate                             811  l-16-fluoro-15(R)-hydroxy-9-                                                                    diazononane                                                                           l-nonyl 16-fluoro-15(R)-                               oxo-5-cis,10,13-trans-pro-                                                                             hydroxy-9-oxo-5-cis,10,13-                             statrienoic acid.sup.1  trans-prostatrienoate                             812  l-16,16-difluoro-15(S)-                                                                         diazohexane                                                                           l-hexyl 16,16-difluoro-15(S)-                          hydroxy-9-oxo-5-cis,10,13-                                                                             hydroxy-9-oxo-5-cis,10,13-                             trans-prostatrienoic acid.sup.1                                                                        trans-prostatrienoate                             813  l-16,16-difluoro-15(S)-                                                                         diazooctane                                                                           l-octyl 16,16-difluoro-15(S)-                          hydroxy-9-oxo-5-cis,10,13-                                                                             hydroxy-9-oxo-5-cis,10,13-                             trans-prostatrienoic acid                                                                              trans-prostatrienoate                             814  l-16,16-difluoro-15(R)-                                                                         diazoheptane                                                                          l-heptyl 16,16-difluoro-15(R)-                         hydroxy-9-oxo-5-cis,10,13-                                                                             hydroxy-9-oxo-5-cis,10,13-                             trans-prostatrienoic acid                                                                              trans-prostatrienoate                             __________________________________________________________________________      .sup.1 Netherlands Patent No. 7,305,817                                  

EXAMPLES 815-821

Hydrogenation of the various prostatrienoic acid esters in Table 22 below in the manner described in Example 52 above is productive of the prostanoic acid esters of the Table.

                                      TABLE 22                                     __________________________________________________________________________          Starting Prostatrienoic                                                                     Product                                                      Example                                                                             Acid Esters of Example                                                                      Prostanoic Acid Esters                                       __________________________________________________________________________     815  808          l-butyl 16-fluoro-15(S)-hydroxy-9-oxo                                          prostanoate                                                  816  809          l-decyl 16-fluoro-15(S)-hydroxy 9-oxo                                          prostanoate                                                  817  810          l-pentyl 16-fluoro-15(R)-hydroxy-9-oxo                                         prostanoate                                                  818  811          l-nonyl 16-fluoro-15(R)-hydroxy-9-oxo                                          prostanoate                                                  819  812          l-hexyl 16,16-difluoro-15(S)-hydroxy-                                          9-oxo prostanoate                                            820  813          l-octyl 16,16-difluoro-15(S)-hydroxy-9-                                        oxo prostanoate                                              821  814          l-heptyl 16,16-difluoro-15(R)-hydroxy-                                         9-oxo prostanoate                                            __________________________________________________________________________

EXAMPLES 822-825

Saponification of the various prostanoate methyl esters of Table 23 below in the manner of Example 58 above is productive of the prostanoic acids of the Table.

                                      TABLE 22                                     __________________________________________________________________________          Starting Prostanoic Acid                                                  Example                                                                             Ester of Example                                                                             Product Prostanoic Acids                                    __________________________________________________________________________     822  764           l-16-fluoro-15(S)-hydroxy-9-                                                   oxoprostanoic acid                                          823  765           l-16-fluoro-15(R)-hydroxy-9-                                                   oxoprostanoic acid                                          824  766           l-16,16-difluoro-15(S)-hydroxy-                                                9-oxoprostanoic acid                                        825  767           l-16,16-difluoro-15(R)-hydroxy-                                                9-oxoprostanoic acid                                        __________________________________________________________________________

EXAMPLE 826 Preparation of l-9α ,15 (S)-dihydroxy-16-fluoro-prostanoic acid

To a solution of 435 mg. of l-16 -fluoro-15(S)-hydroxy-9-oxoprostanoic acid (Example 822) in 4.5 ml. of tetrahydrofuran, stirred in an ice bath under argon atmosphere, is added dropwise 3.7 ml. of 0.76 M lithium perhydro-9b-boraphenalyl hydride. After 40 minutes at 0° C. there is added 1.62 ml. of 3N sodium hydroxide followed by 1.62 ml. of 30% hydrogen peroxide. Ether is added and the resulting solution is acidified with 2N hydrochloric acid. The ether layer is washed several times with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give the subject product as an oil.

EXAMPLES 827-829

Treatment of the 9-oxo-derivative designated in Table 23 below with lithium perhydro-9b-boraphenalyl hydride by the procedure described in Example 826 provides the 9α, 15-dihydroxy derivatives of the Table.

                  TABLE 23                                                         ______________________________________                                                Starting 9-oxo                                                                               Product                                                          prostanoic acid                                                                              9α, 15-dihydroxy                                    Example                                                                               of Example    Derivative                                                ______________________________________                                         827    823           l-9α,15(R)-dihydroxy-                                                    16-fluoroprostanoic                                                            acid                                                      828    824           l-9α,15(S)-dihydroxy-                                                    16,16-difluoropro-                                                             stanoic acid                                              829    825           l-9α,15(R)-dihydroxy-                                                    16,16-difluoropro-                                                             stanoic acid                                              ______________________________________                                    

EXAMPLES 830-836

Treatment of the various prostanoic acids listed in Table 24 below with the indicated diazoalkanes in the manner described in Example 99 above is productive of the esters of the Table.

                                      TABLE 24                                     __________________________________________________________________________          Starting prostanoic                                                       Example                                                                             acid of Example                                                                           Diazoalkane                                                                           Product Prostanoic Acid Ester                           __________________________________________________________________________     830  826        diazomethane                                                                          l-methyl 9α,15(S)-dihydroxy-16-                   fluoroprostanoate                                                              831  826        diazobutane                                                                           l-butyl 9α,15(S)-dihydroxy-15-                                           fluoroprostanoate                                       832  826        diazooctane                                                                           l-octyl 9α,15(S)-dihydroxy-16-                                           fluoroprostanoate                                       833  827        diazopentane                                                                          l-pentyl 9α,15(R)-dihydroxy-16-                                          fluoroprostanoate                                       834  828        diazohexane                                                                           l-hexyl 9α,15(S)-dihydroxy-16,16-                                        difluoroprostanoate                                     835  829        diazoheptane                                                                          l-heptyl 9α,15(R)-dihydroxy-16,16-                                       difluoroprostanoate                                     836  829        diazodecane                                                                           l-decyl 9α,15(R)-dihydroxy-16,16-                                        difluoroprostanoate                                     __________________________________________________________________________

EXAMPLE 837 Preparation of l-9α ,15(S)-dihydroxy-16-fluoro prostanoic acid and 1 9β, 15(S)-dihydroxy-16-fluoroprostanoic acid

To a stirred ice cold solution of 360 mg. of l-16-fluoro-15(S)-hydroxy-9-oxoprostanoic acid (Example 822) in 50 ml. of ethanol is added 409 mg. of sodium borohydride in small portions during 1 minute. The mixture is protected from moisture and is stirred at 0° C. for 5 minutes and at ambient temperature for 6 hours. The bulk of the ethanol is evaporated at room temperature and the residue is treated with ether followed by dilute hydrochloric acid while cooling in an ice bath. The organic phase is separated and washed with water and saturated sodium chloride solution. The solution is dried over anhydrous magnesium sulfate and taken to dryness to give a mixture of the 9α- and 9β-hydroxy compounds which are separated by means of chromatography over acid-washed silica gel.

EXAMPLES 838-840

Treatment of the 9-oxo derivatives listed in Table 25 below with sodium borohydride in accordance with the procedure described in Example 837 is productive of the 9-hydroxy derivatives of the table. Each of these derivatives represents a mixture of 9α- and 9β-hydroxy compounds which are separated by chromatography on acid-washed silica gel.

                  TABLE 25                                                         ______________________________________                                                Starting 9-oxo-                                                                              Product                                                          prostanoic acid                                                                              9α/β,15-dihydroxy                              Example                                                                               of Example    derivative                                                ______________________________________                                         838    823           1-9α/β,15(R)-dihydroxy-                                             16-fluoroprostanoic                                                            acid                                                      839    824           1-9α/β,15(S)-dihydroxy-                                             16,16-difluoropro-                                                             stanoic acid                                              840    825           1-9α/β,15(R)-dihydroxy-                                             16,16-difluoropro-                                                             stanoic acid.                                             ______________________________________                                    

EXAMPLE 841 Preparation of l-methyl 15(S)-acetoxy-9,9-diethoxy prostanoate

A solution of 3 g. of l-methyl 15(S)-acetoxy-9-oxo prostanoate (Example 52) in 20 ml. of absolute ethanol containing 3 ml. of triethylorthoformate and 30 mg. of p-toluene-sulfonic acid is kept at ambient temperature for 18 hours. After flooding with ether the solution is washed with 5% sodium carbonate solution, saturated sodium chloride solution, dried dried with anhydrous sodium sulfate and taken to dryness to furnish 3.5 g. of product.

EXAMPLE 842 Preparation of l-methyl 15(S)-acetoxy-9,9-bis(benzyloxy)-prostanoate

A solution of 2 g. of l-methyl 15(S)-acetoxy-9-oxo prostanoate (Example 52) and 25 mg. of p-toluene sulfonic acid in 65 ml. of benzylalcohol is stirred at 100° C. for 6 hours. The solution is concentrated to near dryness under reduced pressure. The residue is diluted with ether and the resulting solution is washed with 5% sodium carbonate solution, saturated sodium chloride solution, dried with anhydrous sodium sulfate and taken to dryness to afford 2.5 g. of product.

EXAMPLE 843 Preparation of l-9,9-bis(benzyloxy)-15(S)-hydroxy prostanoic acid

In the manner described in Example 58, treatment of l-methyl 15(S)-acetoxy-9,9-bis(benzyloxy)prostanoate (Example 842) with potassium hyroxide in aqueous methanol gives the subject product as an oil. 

I claim:
 1. A compound selected from the group consisting of an optically active compound of the formula: ##STR14##and a racemic compound of that formula and the mirror image thereof wherein Y is a divalent moiety of the formulae: ##STR15##wherein R is hydrogen or lower alkanoyl; n is an integer from 2 to 5, inclusive; R₁ is hydrogen or alkyl having from one to 12 carbon atoms; R₂ is hydrogen or fluorine; and the pharmacologically acceptable cationic salts thereof when R₁ is hydrogen.
 2. The enantiomer according to claim 1, wherein Y is ##STR16## R₁ is hydrogen, n is 3, and R₂ is hydrogen; l-9-oxo-15(S)-hydroxy-16-fluoro-prostanoic acid.
 3. The enantiomer according to claim 1, wherein Y is ##STR17## R₁ is hydrogen, n is 3, and R₂ is hydrogen; l-9-oxo-15(R)-hydroxy-16-fluoro-prostanoic acid.
 4. The enantiomer according to claim 1 wherein Y is ##STR18## R₁ hydrogen, n is 3, and R₂ is fluorine; l-9-oxo-15(S)-hydroxy-16,16-difluoro-prostanoic acid.
 5. The enantiomer according to claim 1 wherein Y is ##STR19## R₁ is hydrogen, n is 3, and R₂ is fluorine; l-9-oxo-15(R)-hydroxy-16,16-difluoro-prostanoic acid.
 6. The enantiomer according to claim 1 wherein Y is ##STR20## R₁ is n-butyl, n is 3, and R₂ is hydrogen; n-butyl l-9-oxo-15(S)-hydroxy-16-fluoro-prostanoate.
 7. The enantiomer according to claim 1 wherein Y is ##STR21## R₁ is n-hexyl, n is 3, and R₂ is fluorine; n-hexyl l-9-oxo-15(S)-hydroxy-16,16-difluoro-prostanoate.
 8. The racemate according to claim 1 wherein Y is ##STR22## R₁ is hydrogen, n is 3, and R₂ is hydrogen; dl-9-oxo-15(S)-hydroxy-16-fluoro-prostanoic acid.
 9. The racemate according to claim 1 wherein Y is ##STR23## R₁ is hydrogen, n is 3, and R₂ is hydrogen; dl-9-oxo-15(R)-hydroxy-16-fluoro-prostanoic acid.
 10. The racemate according to claim 1 wherein Y is ##STR24## R₁ is hydrogen, n is 3, and R₂ is fluorine; dl-9-oxo-15(S)-hydroxy-16,16-difluoro-prostanoic acid.
 11. The racemate according to claim 1 wherein Y is ##STR25## R₁ is hydrogen, n is 3, and R₂ is fluorine; dl-9-oxo-15(R)-hydroxy-16,16-difluoro-prostanoic acid.
 12. The racemate according to claim 1 wherein Y is ##STR26## R₁ is n-butyl, n is 3, and R₂ is hydrogen; n-butyl dl-9-oxo-15(S)-hydroxy-16-fluoro-prostanoate.
 13. The racemate according to claim 1 wherein Y is ##STR27## R₁ is n-hexyl, n is 3, and R₂ is fluorine; n-hexyl dl-9-oxo-15(S)-hydroxy-16,16-difluoro-prostanoate. 